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THE DIAGNOSIS OF PERIPROSTHETIC JOINT

INFECTIONS OF THE HIP AND KNEE

GUIDELINE AND EVIDENCE REPORT

Adopted by the American Academy of Orthopaedic Surgeons

Board of Directors

June 18, 2010

AAOS Clinical Practice Guidelines Unit ii v1.0 062110

Disclaimer

This Clinical Practice Guideline was developed by an AAOS physician volunteer Work

Group based on a systematic review of the current scientific and clinical information and

accepted approaches to treatment and/or diagnosis. This Clinical Practice Guideline is not

intended to be a fixed protocol, as some patients may require more or less treatment or

different means of diagnosis. Clinical patients may not necessarily be the same as those

found in a clinical trial. Patient care and treatment should always be based on a

clinician’s independent medical judgment, given the individual patient’s clinical

circumstances.

Disclosure Requirement

In accordance with AAOS policy, all individuals whose names appear as authors or

contributors to Clinical Practice Guideline filed a disclosure statement as part of the

submission process. All panel members provided full disclosure of potential conflicts of

interest prior to voting on the recommendations contained within this Clinical Practice

Guidelines.

Funding Source

This Clinical Practice Guideline was funded exclusively by the American Academy of

Orthopaedic Surgeons who received no funding from outside commercial sources to

support the development of this document.

FDA Clearance

Some drugs or medical devices referenced or described in this Clinical Practice Guideline

may not have been cleared by the Food and Drug Administration (FDA) or may have

been cleared for a specific use only. The FDA has stated that it is the responsibility of the

physician to determine the FDA clearance status of each drug or device he or she wishes

to use in clinical practice.

Copyright

All rights reserved. No part of this Clinical Practice Guideline may be reproduced, stored

in a retrieval system, or transmitted, in any form, or by any means, electronic,

mechanical, photocopying, recording, or otherwise, without prior written permission

from the AAOS.

Published 2010 by the American Academy of Orthopaedic Surgeons

6300 North River Road

Rosemont, IL 60018

First Edition

Copyright 2010

by the American Academy of Orthopaedic Surgeons

AAOS Clinical Practice Guidelines Unit iii v1.0 062110

Summary of Recommendations The following is a summary of the recommendations in the AAOS’ clinical practice

guideline, The Diagnosis of Periprosthetic Joint Infections of the Hip and Knee. This

summary does not contain rationales that explain how and why these recommendations

were developed nor does it contain the evidence supporting these recommendations. All

readers of this summary are strongly encouraged to consult the full guideline and

evidence report for this information. We are confident that those who read the full

guideline and evidence report will note that the recommendations were developed using

systematic evidence-based processes designed to combat bias, enhance transparency, and

promote reproducibility.

This summary of recommendations is not intended to stand alone. Clinical decisions

should be made in light of all circumstances presented by the patient. Procedures

applicable to the individual patient rely on mutual communication between patient,

physician, and other healthcare practitioners.

1. In the absence of reliable evidence about risk stratification of patients with a

potential periprosthetic joint infection, it is the opinion of the work group that

testing strategies be planned according to whether there is a higher or lower

probability that a patient has a hip or knee periprosthetic infection.

Strength of Recommendation: Consensus

Description: The supporting evidence is lacking and requires the work group to make a

recommendation based on expert opinion by considering the known potential harm and

benefits associated with the treatment. A Consensus recommendation means that expert

opinion supports the guideline recommendation even though there is no available

empirical evidence that meets the inclusion criteria of the guideline’s systematic review.

Implications: Practitioners should be flexible in deciding whether to follow a

recommendation classified as Consensus, although they may set boundaries on

alternatives. Patient preference should have a substantial influencing role.

Note: Please see page 17 of this document for a definition of “higher and lower

probability”.

2. We recommend erythrocyte sedimentation rate and C-reactive protein testing

for patients assessed for periprosthetic joint infection.

Strength of Recommendation: Strong

Description: Evidence is based on two or more “High” strength studies with consistent

findings for recommending for or against the intervention. A Strong recommendation

means that the benefits of the recommended approach clearly exceed the potential harm

(or that the potential harm clearly exceeds the benefits in the case of a strong negative

recommendation), and that the strength of the supporting evidence is high.

AAOS Clinical Practice Guidelines Unit iv v1.0 062110

Implications: Practitioners should follow a Strong recommendation unless a clear and

compelling rationale for an alternative approach is present.

3. We recommend joint aspiration of patients being assessed for periprosthetic

knee infections who have abnormal erythrocyte sedimentation rate AND/OR C-

reactive protein results. We recommend that the aspirated fluid be sent for

microbiologic culture, synovial fluid white blood cell count and differential.









4. We recommend a selective approach to aspiration of the hip based on the

patient’s probability of periprosthetic joint infection and the results of the

erythrocyte sedimentation rate (ESR) AND C-reactive protein (CRP). We

recommend that the aspirated fluid be sent for microbiologic culture, synovial

fluid white blood cell count and differential.

Selection of Patients for Hip Aspiration

Probability of

Infection

ESR and CRP

Results

Planned Reoperation

Status Recommended Test

Higher + + or + − Planned or not planned Aspiration

Lower + + or + − Planned Aspiration or Frozen Section

Lower + + Not planned Aspiration

Lower + − Not planned Please see Recommendation 6

Higher or Lower − − Planned or not planned No further testing

Key for ESR and CRP results

+ + = ESR and CRP test results are abnormal

+ − = either ESR or CRP test result is abnormal

− − = ESR and CRP test results are normal







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5. We suggest a repeat hip aspiration when there is a discrepancy between the

probability of periprosthetic joint infection and the initial aspiration culture

result.

Strength of Recommendation: Moderate

Description: Evidence from two or more “Moderate” strength studies with consistent

findings, or evidence from a single “High” quality study for recommending for or against

the intervention. A Moderate recommendation means that the benefits exceed the

potential harm (or that the potential harm clearly exceeds the benefits in the case of a

negative recommendation), but the strength of the supporting evidence is not as strong.

Implications: Practitioners should generally follow a Moderate recommendation but

remain alert to new information and be sensitive to patient preferences.

6. In the absence of reliable evidence, it is the opinion of the work group that

patients judged to be at lower probability for periprosthetic hip infection and

without planned reoperation who have abnormal erythrocyte sedimentation rates

OR abnormal C-reactive protein levels be re-evaluated within three months. We

are unable to recommend specific diagnostic tests at the time of this follow-up.










AAOS Clinical Practice Guidelines Unit vi v1.0 062110

7. In the absence of reliable evidence, it is the opinion of the work group that a

repeat knee aspiration be performed when there is a discrepancy between the

probability of periprosthetic joint infection and the initial aspiration culture

result.










8. We suggest patients be off of antibiotics for a minimum of 2 weeks prior to

obtaining intra-articular culture.









9. Nuclear imaging (Labeled leukocyte imaging combined with bone or bone

marrow imaging, FDG-PET imaging, Gallium imaging, or labeled leukocyte

imaging) is an option in patients in whom diagnosis of periprosthetic joint

infection has not been established and are not scheduled for reoperation.

Strength of Recommendation: Limited

Description: Evidence from two or more “Low” strength studies with consistent findings,

or evidence from a single “Moderate” quality study recommending for or against the

intervention or diagnostic. A Limited recommendation means the quality of the

supporting evidence that exists is unconvincing, or that well-conducted studies show little

clear advantage to one approach versus another.

Implications: Practitioners should be cautious in deciding whether to follow a

recommendation classified as Limited, and should exercise judgment and be alert to

emerging publications that report evidence. Patient preference should have a substantial

influencing role.

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10. We are unable to recommend for or against computed tomography (CT) or

magnetic resonance imaging (MRI) as a diagnostic test for periprosthetic joint

infection.

Strength of Recommendation: Inconclusive

Description: Evidence from a single low quality study or conflicting findings that do not

allow a recommendation for or against the intervention. An Inconclusive

recommendation means that there is a lack of compelling evidence resulting in an unclear

balance between benefits and potential harm.

Implications: Practitioners should feel little constraint in deciding whether to follow a

recommendation labeled as Inconclusive and should exercise judgment and be alert to

future publications that clarify existing evidence for determining balance of benefits

versus potential harm. Patient preference should have a substantial influencing role.

11. We recommend against the use of intraoperative Gram stain to rule out

periprosthetic joint infection.









12. We recommend the use of frozen sections of peri-implant tissues in patients

who are undergoing reoperation for whom the diagnosis of periprosthetic joint

infection has not been established or excluded.









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13. We recommend that multiple cultures be obtained at the time of reoperation in

patients being assessed for periprosthetic joint infection.









14. We recommend against initiating antibiotic treatment in patients with suspected

periprosthetic joint infection until after cultures from the joint have been

obtained.









15. We suggest that prophylactic preoperative antibiotics not be withheld in patients

at lower probability for periprosthetic joint infection and those with an

established diagnosis of periprosthetic joint infection who are undergoing

reoperation.









AAOS Clinical Practice Guidelines Unit ix v1.0 062110

Work Group Craig Della Valle MD, Chair

Rush University Medical Center

1611 W Harrison St # 300

Chicago, IL 60612-4861

Javad Parvizi, MD, Vice-Chair

Rothman Institute

925 Chestnut St - 5th Fl

Philadelphia, PA 19107

Thomas W Bauer, MD PhD

Cleveland Clinic Foundation

Department of Pathology

9500 Euclid Ave Desk L25

Cleveland, OH 44195

Paul E DiCesare, MD

UC Davis Medical Center

Department of Orthopaedic Surgery

4860 Y St Ste 3800

Sacramento, CA 95817

Richard Parker Evans, MD

University of Arkansas for Medical Sciences

Department of Orthopedics

4301 W Markham, #531

Little Rock, AR 72205

John Segreti, MD


600 S Paulina St. Ste 143

Chicago, Il 60612

Mark Spangehl, MD

Mayo Clinic

5777 East Mayo Blvd

Phoenix, AZ 85054

Guidelines and Technology Oversight

Chair:

William C. Watters III MD 6624 Fannin #2600

Houston, TX 77030

Evidence Based Practice Committee Chair:

Michael Keith, MD

2500 Metro Health Drive

Cleveland, OH 44109-1900

AAOS Staff:

Charles M. Turkelson, PhD Director of Research and Scientific Affairs

6300 N River Road

Rosemont, IL 60018

Janet L. Wies MPH

AAOS Clinical Practice Guideline Mgr

Patrick Sluka MPH

AAOS Research Analyst

Kristin Hitchcock, MSI

AAOS Medical Librarian

Special Acknowledgements

Sara Anderson MPH

Kevin Boyer

Laura Raymond, MA

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Peer Review Participation in the AAOS peer review process does not constitute an endorsement

of this guideline by the participating organization.

The following organizations participated in peer review of this clinical practice guideline

and gave explicit consent to be listed in this document:

American Association of Hip and Knee Surgeons

European Bone and Joint Infection Society

Knee Society

Musculoskeletal Infection Society

Society of Nuclear Medicine

Participation in the AAOS peer review process does not constitute an endorsement


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Table of Contents

SUMMARY OF RECOMMENDATIONS .............................................................. III

WORK GROUP .................................................................................................. IX

PEER REVIEW .................................................................................................... X

TABLE OF CONTENTS ..................................................................................... XI

LIST OF FIGURES ............................................................................................ XV

LIST OF TABLES ............................................................................................. XVI

I. INTRODUCTION ........................................................................................... 1

Overview........................................................................................................................................................ 1

Goals and Rationale ..................................................................................................................................... 1

Intended Users .............................................................................................................................................. 1

Patient Population ........................................................................................................................................ 2

Etiology .......................................................................................................................................................... 2

Incidence ....................................................................................................................................................... 2

Burden of Disease ......................................................................................................................................... 2

Risk Factors .................................................................................................................................................. 2

Emotional and Physical Impact ................................................................................................................... 2

Potential Benefits and Harms ...................................................................................................................... 2

II. METHODS ..................................................................................................... 3

Formulating Preliminary Recommendations ............................................................................................. 3

Study Selection Criteria ............................................................................................................................... 3 Inclusion of studies with mixed patient populations .................................................................................. 4 Best Available Evidence ............................................................................................................................ 4

Literature Searches ...................................................................................................................................... 4

Data Extraction ............................................................................................................................................. 5

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Judging the Quality of Evidence ................................................................................................................. 5 Diagnostic Studies ..................................................................................................................................... 5 Prognostic Studies ..................................................................................................................................... 7

Defining the Strength of the Recommendations ........................................................................................ 7

Consensus Development ............................................................................................................................... 9

Statistical Methods ....................................................................................................................................... 9

Peer Review ..................................................................................................................................................10

Public Commentary.....................................................................................................................................10

The AAOS Guideline Approval Process ....................................................................................................10

Revision Plans ..............................................................................................................................................11

Guideline Dissemination Plans ...................................................................................................................11

III. ALGORITHMS ......................................................................................... 12

IV. RECOMMENDATIONS AND SUPPORTING DATA ............................... 15

Recommendation 1 ......................................................................................................................................15 Summary of Evidence ...............................................................................................................................18 Excluded Articles......................................................................................................................................21 Study Quality ............................................................................................................................................34 Study Results ............................................................................................................................................40




Recommendation 5 ....................................................................................................................................103 Excluded Articles....................................................................................................................................104 Study Quality ..........................................................................................................................................105 Study Results ..........................................................................................................................................105

Recommendation 6 ....................................................................................................................................106

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Recommendation 7 ....................................................................................................................................108 Excluded Articles....................................................................................................................................108

Recommendation 8 ....................................................................................................................................110 Excluded Articles....................................................................................................................................111 Study Quality ..........................................................................................................................................112 Study Results ..........................................................................................................................................112

Recommendation 9 ....................................................................................................................................113 Summary of Evidence .............................................................................................................................117 Excluded Articles....................................................................................................................................118 Study Quality ..........................................................................................................................................127 Study Results ..........................................................................................................................................132

Recommendation 10 ..................................................................................................................................150 Summary of Evidence .............................................................................................................................150 Excluded Articles....................................................................................................................................151 Study Quality ..........................................................................................................................................152 Study Results ..........................................................................................................................................154




Recommendation 14 ..................................................................................................................................194 Excluded Articles....................................................................................................................................195 Study Quality ..........................................................................................................................................196 Study Results ..........................................................................................................................................197

Recommendation 15 ..................................................................................................................................198 Excluded Articles....................................................................................................................................199 Study Quality ..........................................................................................................................................202 Study Results ..........................................................................................................................................204

Future Research ........................................................................................................................................206

V. APPENDIXES ............................................................................................ 208

Appendix I ..................................................................................................................................................209 Work Group ............................................................................................................................................209

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Appendix II ................................................................................................................................................210 AAOS Bodies That Approved This Clinical Practice Guideline ............................................................210 Documentation of Approval ...................................................................................................................211

Appendix III ...............................................................................................................................................212 Study Attrition Flowchart .......................................................................................................................212

Appendix IV ...............................................................................................................................................213 Literature Searches .................................................................................................................................213

Appendix V ................................................................................................................................................216 Data Extraction Elements .......................................................................................................................216

Appendix VI ...............................................................................................................................................217 Judging the Quality of Diagnostic Studies ..............................................................................................217 Judging the Quality of Prognostic Studies ..............................................................................................218 Judging the Quality of Treatment Studies ..............................................................................................218

Appendix VII .............................................................................................................................................219 Form for Assigning Strength of Recommendation (Interventions) ........................................................219

Appendix VIII ............................................................................................................................................221 Voting by the Nominal Group Technique ..............................................................................................221 Opinion-Based Recommendations .........................................................................................................221

Appendix IX ...............................................................................................................................................224 Structured Peer Review Form .................................................................................................................224

Appendix X ................................................................................................................................................227 Peer Review Panel ..................................................................................................................................227 Public Commentary ................................................................................................................................228

Appendix XI ...............................................................................................................................................229 Interpreting the Forest Plots ....................................................................................................................229

Appendix XII .............................................................................................................................................230 Conflict of Interest ..................................................................................................................................230

Appendix XIII ............................................................................................................................................232 References ..............................................................................................................................................232 Articles Excluded from the Systematic Review(s) .................................................................................242

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List of Figures Algorithm for Patients with Higher Probability of Hip or Knee Periprosthetic Joint

Infection ................................................................................................................ 12

Algorithm for Patients with Lower Probability of Periprosthetic Knee Infection ............ 13 Algorithm for Patients with Lower Probability of Periprosthetic Hip Infection with

Planned Reoperation ............................................................................................. 14 Algorithm for Patients with Lower Probability of Periprosthetic Hip Infection without

Planned Reoperation ............................................................................................. 14

ESR Meta-analysis Results - Likelihood Ratios ............................................................... 56 CRP Results - Likelihood Ratios ...................................................................................... 57

ESR and CRP - Likelihood Ratios .................................................................................... 57

Radiography Results - Likelihood Ratios ......................................................................... 58 White Blood Cell Count Results - Likelihood Ratios ....................................................... 58 Hip Aspiration Cultures Results - Meta-Analysis ............................................................ 94 Synovial Fluid WBC Count Results - Likelihood Ratios (Hip and Knee) ....................... 95

Neutrophil Percentage Results – Likelihood Ratios (Hip and Knee) ............................... 95 Technetium-labeled-Leukocyte Imaging Results – Likelihood Ratios .......................... 132

Indium-labeled-Leukocyte Imaging Results - Likelihood Ratios ................................... 133 Combined Leukocyte/Bone Imaging Results – Likelihood Ratios................................. 133 Combined Leukocyte/Bone Marrow Imaging Results - Likelihood Ratios ................... 134

FDG-PET Imaging Results - Likelihood Ratios ............................................................. 134

Technetium-99m Bone Imaging Results - Likelihood Ratios ........................................ 135 Other Nuclear Imaging Results - Likelihood Ratios....................................................... 136 CT Imaging Results - Likelihood Ratios ........................................................................ 154

Gram Stain Results - Likelihood Ratios ......................................................................... 160 Frozen Section Meta-Analysis – Threshold of 10 PMN in 5 Fields ............................... 170

Frozen Section Meta-Analysis – Threshold of 5 PMN/HPF .......................................... 170 Frozen Section Results - Likelihood Ratios – Mixed Thresholds .................................. 171 Intraoperative Cultures Results - Threshold of 1 vs. 2 Positive Cultures ....................... 183

Intraoperative Cultures Results - Tissue or Swab or Fluid ............................................. 183

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List of Tables Reference Standard Used in Included Diagnostic Studies .................................................. 6 Strength of recommendation descriptions .......................................................................... 8

AAOS Guideline Language ................................................................................................ 9 Interpreting Likelihood Ratios .......................................................................................... 10 Results of Prognostic Studies - Hip .................................................................................. 18 Results of Prognostic Studies - Knee ................................................................................ 19 Summary of Evidence – Diagnostic or Prevalence Studies .............................................. 20

Excluded Articles - Recommendation 1 ........................................................................... 21 Quality of Diagnostic Studies ........................................................................................... 34

Quality of Prognostic Studies ........................................................................................... 35

Risk Factors - Quality of Joint Registries ......................................................................... 38 Risk Factors - Quality of Randomized Trials ................................................................... 39 Pain as a Predictor of Periprosthetic Infection .................................................................. 40 Warmth, Erythema, Swelling as Predictors of Periprosthetic Infection ........................... 40

Early Implant Failure as a Predictor of Periprosthetic Infection ...................................... 41 Sinus Tract as a Predictor of Periprosthetic Infection ...................................................... 41

Prevalence of Periprosthetic Infection among Patients with Bacteremia ......................... 41 Prevalence of Periprosthetic Infection among Patients with Metachronous Periprosthetic

Infection ................................................................................................................ 42

Anticoagulation RCT ........................................................................................................ 42

Use of Drains RCTs .......................................................................................................... 43 Radiography and Serology Summary of Evidence ........................................................... 46 Excluded Articles - Recommendation 2 ........................................................................... 47

Radiography and Serology - Quality ................................................................................ 51 Erythrocyte Sedimentation Rate Results .......................................................................... 59

C-Reactive Protein Results ............................................................................................... 62 ESR and CRP Results ....................................................................................................... 65 Radiography Results ......................................................................................................... 67

White Blood Cell Count Results ....................................................................................... 70 Knee Aspiration Summary of Evidence ........................................................................... 76 Excluded Articles - Recommendation 3 ........................................................................... 77

Knee Aspiration - Quality ................................................................................................. 78

Aspiration Culture - Knee ................................................................................................. 79

Synovial Fluid White Blood Cell Count ........................................................................... 80 Synovial Fluid Neutrophil Percentage .............................................................................. 83 Aspiration Summary of Evidence ..................................................................................... 87 Excluded Articles - Recommendation 4 ........................................................................... 89 Aspiration - Quality .......................................................................................................... 92

Aspiration Culture - Hip ................................................................................................... 96 Synovial Fluid White Blood Cell Count ........................................................................... 98 Synovial Fluid Neutrophil Percentage ............................................................................ 101 Excluded Articles - Recommendation 5 ......................................................................... 104 Repeat Aspiration - Quality ............................................................................................ 105

Repeat Aspiration Results ............................................................................................... 105

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Excluded Article - Recommendation 7 ........................................................................... 108 Excluded Articles - Recommendation 8 ......................................................................... 111 Preoperative Antibiotic Therapy - Quality ..................................................................... 112 Preoperative Antibiotics and False-Negative Cultures ................................................... 112

Nuclear Imaging Summary of Evidence ......................................................................... 117 Excluded Articles - Recommendation 9 ......................................................................... 118 Nuclear Imaging - Quality .............................................................................................. 127 Technetium-99m-labeled-Leukocyte Imaging................................................................ 137 Indium-111-labeled-Leukocyte Imaging ........................................................................ 139

Combined Leukocyte/Bone Imaging .............................................................................. 140 Combined Leukocyte/Bone Marrow Imaging ................................................................ 142 Gallium-67 Imaging ........................................................................................................ 145

FDG-PET Imaging .......................................................................................................... 146 Technetium-99m Bone Imaging ..................................................................................... 148 Other Nuclear Imaging tests ........................................................................................... 149

CT and MRI Summary of Evidence ............................................................................... 150 Excluded Articles - Recommendation 10 ....................................................................... 151

Study Quality - CT .......................................................................................................... 152 CT Imaging ..................................................................................................................... 155 Gram Stain Summary of Evidence ................................................................................. 157

Excluded Articles - Recommendation 11 ....................................................................... 158 Gram Stain - Quality ....................................................................................................... 159

Intraoperative Gram Stain Results .................................................................................. 161

Frozen Section Summary of Evidence ............................................................................ 165

Excluded Articles - Recommendation 12 ....................................................................... 166 Frozen Section - Quality ................................................................................................. 168

Frozen Section Results .................................................................................................... 172 Summary of Evidence ..................................................................................................... 177 Excluded Articles - Recommendation 13 ....................................................................... 178

Intraoperative Cultures - Quality .................................................................................... 181 Overall and number of cultures results ........................................................................... 184

Tissue vs. Swab vs. Fluid ................................................................................................ 191 Excluded Articles - Recommendation14 ........................................................................ 195

Preoperative Antibiotic Therapy - Quality ..................................................................... 196

Preoperative Antibiotics and False-Negative Cultures ................................................... 197

Excluded Articles - Recommendation 15 ....................................................................... 199 Preoperative Antibiotics - Diagnostic Study Quality...................................................... 202 Preoperative Antibiotics - Randomized Trial Quality .................................................... 203 Preoperative Antibiotics - Joint Registry Quality ........................................................... 203 Preoperative Antibiotics and False-Negative Cultures ................................................... 204

Relative Risk of Infection - Placebo vs. Preoperative Antibiotics.................................. 204 Registry Data – Hazard Ratio of Revision due to Infection ........................................... 205

AAOS Clinical Practice Guideline Unit v1.0 062110 1

I. INTRODUCTION

OVERVIEW This clinical practice guideline is based on a systematic review of published studies on

the diagnosis of periprosthetic joint infections of the hip and knee. In addition to

providing practice recommendations, this guideline also highlights gaps in the literature

and areas that require future research.

This guideline is intended to be used by all appropriately trained surgeons and all

qualified physicians evaluating patients for periprosthetic joint infections of the hip and

knee. It is also intended to serve as an information resource for decision makers and

developers of practice guidelines and recommendations.

GOALS AND RATIONALE The purpose of this clinical practice guideline is to help improve treatment based on the

current best evidence. Current evidence-based practice (EBP) standards demand that

physicians use the best available evidence in their clinical decision making. This clinical

practice guideline was developed following systematic review of the available literature

regarding the diagnosis of periprosthetic infections of the hip and the knee. The

systematic review detailed herein was conducted between October 2008 and September

2009 and demonstrates where there is good evidence, where evidence is lacking, and

what topics future research must target in order to improve the diagnosis of periprosthetic

joint infections of the hip and knee. AAOS staff and the physician work group

systematically reviewed the available literature and subsequently wrote the following

recommendations based on a rigorous, standardized process.

Musculoskeletal care is provided in many different settings by many different providers.

We created this guideline as an educational tool to guide qualified physicians through a

series of diagnostic decisions in an effort to improve the quality and efficiency of care.

This guideline should not be construed as including all proper methods of care or

excluding methods of care reasonably directed to obtaining the same results. The ultimate

judgment regarding any specific procedure or treatment must be made in light of all

circumstances presented by the patient and the needs and resources particular to the

locality or institution. Further, the scope of the guideline does not include information on

laboratory techniques or tissue sampling techniques beyond the evidence presented to

support Recommendations 13 and 14. It is assumed that the well qualified physician will

use his/her best judgement, considering the individual patient circumstances as well as

the available resources, when addressing these issues.

INTENDED USERS This guideline is intended to be used by orthopaedic surgeons and all qualified physicians

managing the diagnosis of periprosthetic joint infections of the hip and knee. Typically,

orthopaedic surgeons will have completed medical training, a qualified residency in

orthopaedic surgery, and some may have completed additional sub-specialty training. It is

also intended to serve as an information resource for professional healthcare practitioners

and developers of practice guidelines and recommendations.


PATIENT POPULATION This document addresses the diagnosis of periprosthetic joint infections in patients who

have undergone arthroplasty of the hip or knee This guideline is not intended for patients

with superficial infections.

ETIOLOGY Periprosthetic joint infection can be caused by entry of organisms into the wound during

surgery, hematogenous spread, recurrence of sepsis in a previously infected joint, or

contiguous spread of infection from a local source.22

INCIDENCE The incidence of periprosthetic joint infection after primary hip or knee arthroplasty is

over 2% among the Medicare population.56, 76

The incidence of periprosthetic infection is

higher after revision arthroplasty than after primary arthroplasty in both joints.64, 82

BURDEN OF DISEASE Periprosthetic joint infection requires significant resources to diagnose and treat.

Infection is a common cause of revision arthroplasty, with 15% of revision total hip

arthroplasties and 25% of revision total knee arthroplasties being due to infection.12, 13

RISK FACTORS Risk factors identified and supported by the evidence include prior infection of the joint

(knee), superficial surgical site infection (hip and knee), obesity (hip), extended operative

time (>2.5 hours, hip and knee) and immunosuppression (knee). The work group also

discusses additional risk factors based on consensus in Recommendation 1.

EMOTIONAL AND PHYSICAL IMPACT Periprosthetic joint infection is a serious complication of total joint replacement resulting

in significant morbidity, including pain, loss of function, and potential removal of the

prosthesis.

POTENTIAL BENEFITS AND HARMS There is the possibility of harm resulting from diagnostic tests, including the possibility

of the introduction of bacteria into the joint during an aspiration and patient pain and/or

discomfort while undergoing the procedure. Therefore, discussion of available diagnostic

procedures applicable to the individual patient rely on mutual communication between

the patient and physician, weighing the potential risks and benefits for that patient.


II. METHODS

This section describes the methods used to prepare this guideline and systematic review,

including search strategies used to identify literature, criteria for selecting eligible

articles, determining the strength of the evidence, data extraction, methods of statistical

analysis, and the review and approval of the guideline. The methods used to perform this

systematic review were employed to minimize bias in the selection and analysis of the

available evidence.17, 69

This is vital to the development of reliable, transparent, and

accurate clinical recommendations for diagnosing periprosthetic joint infections of the

hip and knee.

The AAOS Diagnosis of Periprosthetic Joint Infections of the Hip and Knee physician

work group prepared this guideline and systematic review with the assistance of the

AAOS Clinical Practice Guidelines Unit in the Department of Research and Scientific

Affairs at the AAOS (Appendix I).

To develop this guideline, the work group held an introductory meeting to develop the

scope of the guideline on October 17 and 18, 2008. Upon completion of the systematic

review, the work group met again on September 12 and 13, 2009 to write and vote on the

final recommendations and rationales for each recommendation. The resulting draft

guidelines were then peer-reviewed, subsequently sent for public commentary, and then

sequentially approved by the AAOS Evidence Based Practice Committee, AAOS

Guidelines and Technology Oversight Committee, AAOS Council on Research, Quality

Assessment, and Technology, and the AAOS Board of Directors (see Appendix II for a

description of the AAOS bodies involved in the approval process)

FORMULATING PRELIMINARY RECOMMENDATIONS The work group began work on this guideline by constructing a set of preliminary

recommendations. These recommendations specify [what] should be done in [whom],

[when], [where], and [how often or how long]. They function as questions for the

systematic review, not as final recommendations or conclusions. Preliminary

recommendations are almost always modified on the basis of the results of the systematic

review. Once established, these a priori preliminary recommendations cannot be

modified until the final work group meeting, they must be addressed by the systematic

review, and the relevant review results must be presented in the final guideline.

STUDY SELECTION CRITERIA We developed a priori article inclusion criteria for our review. These criteria are our

“rules of evidence” and articles that do not meet them are, for the purposes of this

guideline, not evidence.

To be included in our systematic reviews (and hence, in this guideline) an article had to

be a report of a study that:

Addressed the value of tests for diagnosis of periprosthetic joint infection in

the hip and knee.


Was written in English and published in or after 1970. For MRI, CT and PET

only studies published after 2000 were included. For other nuclear imaging

modalities, only studies published after 1975 were considered.

Was not an abstract, unpublished study report, letter, case report, historical

article, editorial, tutorial, traditional review or commentary.

Was published in the peer-reviewed literature.

Was not a cadaveric, animal, or an in vitro study.

Included 25 or more patients per study arm.

Reported sufficient data to construct a 2 x 2 table.

Was of the highest level of available evidence (best available evidence),

assuming that there were two or more studies of that higher level. Hip and

knee studies were considered separately. For example, if there were two Level

II studies of the hip and two Level II studies of the knee that addressed the

recommendation Level III and IV studies were not included.

Was not evaluating a test in a cohort where the infected prosthesis had already

been removed (no more than 10% of cohort or data from these patients

reported separately).

INCLUSION OF STUDIES WITH MIXED PATIENT POPULATIONS

The work group specified a priori to the literature search that data would be stratified by

joint but that mixed studies could be accepted and reported as such.

BEST AVAILABLE EVIDENCE

When examining primary studies, we analyzed the best available evidence regardless of

study design. We first considered the randomized controlled trials identified by the search

strategy. In the absence of two or more RCTs, we sequentially searched for prospective

controlled trials, prospective comparative studies, retrospective comparative studies, and

prospective case-series studies. Only studies of the highest level of available evidence

were included, assuming that there were 2 or more studies of that higher level. For

example, if there were two Level II studies that addressed the recommendation, Level III

and IV studies were not included.

LITERATURE SEARCHES We attempted to make our searches for articles comprehensive. Using comprehensive

literature searches ensures that the evidence we considered for this guideline is not biased

for (or against) any particular point of view.

We searched for articles published from January 1970 to August 10, 2009. Strategies for

searching electronic databases were constructed by a Medical Librarian to identify


relevant clinical studies. We searched four electronic databases; PubMed, EMBASE,

CINAHL, and The Cochrane Central Register of Controlled Trials.

All searches of electronic databases were supplemented with manual screening of the

bibliographies of all retrieved publications. We also searched the bibliographies of recent

systematic reviews and other review articles for potentially relevant citations. Finally,

work group members provided a list of potentially relevant studies that were not

identified by our searches. All articles identified were subject to the study selection

criteria listed above.

The study attrition diagram in Appendix III provides details about the inclusion and

exclusion of the studies considered for this guideline. The search strategies used to

identify these studies are provided in Appendix IV.

DATA EXTRACTION Data elements extracted from studies were defined in consultation with the physician

work group. One analyst completed data extraction for all studies. The elements extracted

are shown in Appendix V. Evidence tables were constructed to summarize the best

evidence pertaining to each preliminary recommendation. Disagreements about the

accuracy of extracted data were resolved by discussion and consulting the physician work

group.

The work group specified a priori to the literature search that data would be stratified by

joint but that mixed studies could be accepted and reported as such. When studies did not

separate the data by joint, we could not report them separately. If a study with mixed

joints reported the data for each joint we reported them as such. If a study reported

mixed joints but had fewer than 25 patients per joint, only the mixed data was reported.

JUDGING THE QUALITY OF EVIDENCE Determining the quality of the included evidence is vitally important when preparing any

evidence-based work product. Doing so conveys the amount of confidence one can have

in any study’s results. One has more confidence in high quality evidence than in low

quality evidence.

Assigning a level of evidence on the basis of study design plus other quality

characteristics ties the levels of evidence we report more closely to quality than levels of

evidence based only on study design. Because we tie quality to levels of evidence, we are

able to characterize the confidence one can have in their results. Accordingly, we

characterize the confidence one can have in Level I evidence as high, the confidence one

can have in Level II and III evidence as moderate, and the confidence one can have in

Level IV and V evidence as low. Similarly, throughout the guideline we refer to Level I

evidence as reliable, Level II and III evidence as moderately reliable, and Level IV and V

evidence as not reliable.

DIAGNOSTIC STUDIES

We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) instrument

to identify potential bias and assess variability and the quality of reporting in studies


reporting the effectiveness of diagnostic techniques.109

Studies without any indication of

bias are categorized as Level I studies. Studies with a known bias are downgraded to

Level IV or Level III (for a bias for which we have or have not found published evidence

that this bias affects diagnostic results, respectively). Studies with more than one bias are

downgraded to Level V. Those studies that do not sufficiently report their methods for a

potential bias are downgraded to Level II since we are unable to determine if the bias did

or did not bias the results of the study (see Appendix VI).

Although the definition of a reference standard varies in the periprosthetic joint infection

literature, intraoperative cultures have been used most often as the reference standard in

interpreting the results of a diagnostic test, as indicated in Table 1. Accordingly, when

possible we also used intraoperative cultures as a reference standard when computing

measures of test performance.

Table 1. Reference Standard Used in Included Diagnostic Studies

Reference Standard

(Infection defined as positive results on following test(s)) Number of Studies

Intraoperative cultures 18

Intraoperative cultures and histology 7

Histology 4

At least 2 of intraoperative cultures, purulence, and histology 4

Intraoperative cultures or histology 3

Open wound or sinus communicating with the joint OR systemic

infection with pain in the hip and purulent fluid within the joint

OR positive result on at least 3 tests (ESR, CRP, joint aspiration,

intraoperative frozen section, and intraoperative culture)

3

Histology or purulence or sinus tract communicating with the

prosthesis 2

Intraoperative cultures or purulence 2

Aspiration or intraoperative cultures 1

At least 2 of intraoperative cultures, purulence, and histology; or

2 positive cultures 1

Histology and gross operative findings 1

Intraoperative cultures or histology or purulence 1

Intraoperative cultures or histology or deep abscess 1

Cultures or purulence or histology or sinus tract communicating

with the prosthesis 1

Correlation between intraoperative cultures and histology; the

appearance of the tissue intraoperatively; and the clinical course 1

Intraoperative cultures and gross sepsis 1

At least 3 of CRP, ESR, aspiration culture, intraoperative

purulence, intraoperative culture 1


Reference Standard

(Infection defined as positive results on following test(s)) Number of Studies

Abscess or sinus tract communicating with the joint space OR

aspiration culture OR ≥2 intraoperative cultures OR 1 culture and

purulence or histology OR purulence and histology

1

PROGNOSTIC STUDIES

In studies investigating the effect of a characteristic on the outcome of disease, we

assessed quality using a two-step process. Any study that investigated a prospectively

enrolled cohort of patients and utilized regression analysis was initially categorized as a

Level I study. A study that used regression analysis in a retrospectively enrolled cohort of

patients was categorized as a Level II study. A case-control study that used regression

analysis was categorized as a Level III study. We next assessed the outcome (dependent

variable) for each prognostic factor (independent variable) using a quality questionnaire

and, when quality standards were not met, we downgraded the level of evidence by one

level (Appendix VI).

DEFINING THE STRENGTH OF THE RECOMMENDATIONS Judging the quality of evidence is only a stepping stone towards arriving at the strength

of a guideline recommendation. Unlike Levels of Evidence (which apply only to a given

result at a given follow-up time in a given study) strength of recommendation takes into

account the quality, quantity, and applicability of the available evidence. Strength also

takes into account the trade-off between the benefits and harms of a treatment or

diagnostic procedure, and the magnitude of a treatment’s effect.

Strength of recommendation expresses the degree of confidence one can have in a

recommendation. As such, the strength expresses how possible it is that a

recommendation will be overturned by future evidence. It is very difficult for future

evidence to overturn a recommendation that is based on many high quality randomized

controlled trials that show a large effect. It is much more likely that future evidence will

overturn recommendations derived from a few small case series. Consequently,

recommendations based on the former kind of evidence are given a high strength of

recommendation and recommendations based on the latter kind of evidence are given a

low strength.

To develop the strength of a recommendation, AAOS staff first assigned a preliminary

strength for each recommendation that took only the quality and quantity of the available

evidence into account (see Table 2). Work group members then modified the preliminary

strength using the ‘Form for Assigning Strength of Recommendation (Interventions)’

shown in Appendix VII.


Table 2 Strength of recommendation descriptions

1 The AAOS will issue a consensus-based recommendation only when the service in question has virtually no

associated harm and is of low cost (e.g. a history and physical) or when not establishing a recommendation could have

catastrophic consequences.

Statement

Rating

Description of Evidence Strength Implication for Practice

Strong

Evidence is based on two or more “High” strength studies

with consistent findings for recommending for or against the

intervention.

A Strong recommendation means that the benefits of the

recommended approach clearly exceed the potential harm (or

that the potential harm clearly exceeds the benefits in the case

of a strong negative recommendation), and that the strength

of the supporting evidence is high.

Practitioners should follow a Strong

recommendation unless a clear and compelling

rationale for an alternative approach is present.

Moderate

Evidence from two or more “Moderate” strength studies with

consistent findings, or evidence from a single “High” quality

study for recommending for or against the intervention.

A Moderate recommendation means that the benefits exceed

the potential harm (or that the potential harm clearly exceeds

the benefits in the case of a negative recommendation), but

the strength of the supporting evidence is not as strong.

Practitioners should generally follow a

Moderate recommendation but remain alert to

new information and be sensitive to patient

preferences.

Limited

Evidence from two or more “Low” strength studies with

consistent findings, or evidence from a single Moderate

quality study recommending for or against the intervention or

diagnostic.

A Limited recommendation means the quality of the

supporting evidence that exists is unconvincing, or that well-

conducted studies show little clear advantage to one approach

versus another.

Practitioners should be cautious in deciding

whether to follow a recommendation classified

as Limited, and should exercise judgment and

be alert to emerging publications that report

evidence. Patient preference should have a

substantial influencing role.

Inconclusive Evidence from a single low quality study or conflicting

findings that do not allow a recommendation for or against

the intervention.

An Inconclusive recommendation means that there is a lack

of compelling evidence resulting in an unclear balance

between benefits and potential harm.

Practitioners should feel little constraint in

deciding whether to follow a recommendation

labeled as Inconclusive and should exercise

judgment and be alert to future publications that

clarify existing evidence for determining balance

of benefits versus potential harm. Patient

preference should have a substantial influencing

role.

Consensus1

The supporting evidence is lacking and requires the work

group to make a recommendation based on expert opinion by

considering the known potential harm and benefits associated

with the treatment.

A Consensus recommendation means that expert opinion

supports the guideline recommendation even though there is

no available empirical evidence that meets the inclusion

criteria.

Practitioners should be flexible in deciding

whether to follow a recommendation classified

as Consensus, although they may set boundaries

on alternatives. Patient preference should have a

substantial influencing role.


Each recommendation was written using language that accounts for the final strength of

the recommendation. This language, and the corresponding strength, is shown in Table 3.

Table 3. AAOS Guideline Language

Guideline Language

Strength of

Recommendation

We recommend Strong

We suggest Moderate

option Limited

We are unable to recommend for or against Inconclusive

In the absence of reliable evidence, it is the

opinion of this work group Consensus

CONSENSUS DEVELOPMENT The recommendations and their strength were voted on using a structured voting

technique known as the nominal group technique.71

We present details of this technique

in Appendix VIII. Voting on guideline recommendations was conducted using a secret

ballot and workgroup members were blinded to the responses of other members. If

disagreement between workgroup members was significant, there was further discussion

to see whether the disagreement(s) could be resolved. Up to three rounds of voting were

held to attempt to resolve disagreements. If disagreements were not resolved following

three voting rounds, no recommendation was adopted. Lack of agreement is a reason that

the strength for some recommendations are labeled as “Inconclusive.”

STATISTICAL METHODS Likelihood ratios, sensitivity, specificity and 95% confidence intervals were used to

determine the accuracy of diagnostic modalities based on two by two diagnostic

contingency tables extracted from the included studies. When possible, prognostic factors

were analyzed according to sensitivity and specificity as well.80

Likelihood ratios (LR)

indicate the magnitude of the change in probability of disease due to a given test result.

For example, a positive likelihood ratio of 10 indicates that a positive test result is 10

times more common in patients with disease than in patients without disease. Likelihood

ratios are interpreted according to previously published values, as seen in Table 4.42

Likelihood ratios, sensitivity, specificity and 95% confidence intervals were calculated in

STATA 10.0 (StataCorp LP, College Station, Texas). For meta-analysis of diagnostic

tests, we used the bivariate random effects model.38, 39, 89

Meta-analyses were conducted

only if there were at least four studies for a given diagnostic test. When a meta-analysis

indicated between-study heterogeneity (I2 >50%) and thresholds for a positive test result

varied between studies, we included the threshold as a covariate in the model to

determine whether the heterogeneity could be explained by the variation in thresholds.


Table 4. Interpreting Likelihood Ratios

Positive

Likelihood Ratio

Negative

Likelihood Ratio Interpretation

>10 <0.1 Large and conclusive change in probability

5-10 0.1-0.2 Moderate change in probability

2-5 0.2-0.5 Small (but sometimes important) change in

probability

1-2 0.5-1 Small (and rarely important) change in

probability

PEER REVIEW The draft of this guideline and evidence report was peer reviewed by an expert, outside

advisory panel that was nominated a priori by the physician work group prior to the

development of the guideline. The physician members of the AAOS Guidelines and

Technology Oversight Committee and the Evidence Based Practice Committee also

provided peer review of the draft document. Peer review was accomplished using a

structured peer review form (see Appendix IX). The draft guideline was sent to a total of

11 reviewers and 10 of these members returned reviews (see Appendix X) within the

designated time frame. The disposition of all non-editorial peer review comments was

documented and accompanied this guideline through the public commentary and the

AAOS guideline approval process.

PUBLIC COMMENTARY After modifying the draft in response to peer review, the guideline was subjected to a

thirty day period of “Public Commentary.” Commentators consist of members of the

AAOS Board of Directors (BOD), members of the Council on Research, Quality

Assessment, and Technology (CORQAT), members of the Board of Councilors (BOC),

and members of the Board of Specialty Societies (BOS). Based on these bodies, up to

185 commentators had the opportunity to provide input into this guideline development

process. Of these, 10 members of the BOC and 7 members of the BOS requested that we

send them the document during the period of public comment. In addition, the Executive

Directors of the Hip Society and the Orthopaedic Trauma Association each requested that

we send additional drafts to two of their members. A member of the IDSA also requested

the opportunity to provide comment on the draft and was forwarded all materials. One of

these 22 members returned public comments. The single peer reviewer who did not return

his comments during the time frame for peer review returned his comments during the

period of public comment. We responded to both of these revewers’ comments. (see

Appendix X).

THE AAOS GUIDELINE APPROVAL PROCESS Following public commentary, the draft was again modified by the AAOS Clinical

Practice Guidelines Unit and work group members. This final guideline draft was

approved by the AAOS Guidelines Oversight Committee, the AAOS Evidence Based


Practice Committee, the AAOS Council on Research, Quality Assessment, and

Technology, and the AAOS Board of Directors. Descriptions of these bodies are provided

in Appendix II.

REVISION PLANS This guideline represents a cross-sectional view of current diagnosis and may become

outdated as new evidence becomes available. The AAOS may revise this guideline in

accordance with new evidence, changing practice, rapidly emerging treatment options, or

new technology. This guideline will be updated or withdrawn in five years in accordance

with the standards of the National Guideline Clearinghouse.

GUIDELINE DISSEMINATION PLANS The primary purpose of the present document is to provide interested readers with full

documentation about not only our recommendations, but also about how we arrived at

those recommendations. This document is also posted on the AAOS website at

http://www.aaos.org/research/guidelines/guide.asp.

Shorter versions of the guideline are available in other venues. Publication of most

guidelines is announced by an Academy press release, articles authored by the work

group and AAOS staff and published in the Journal of the American Academy of

Orthopaedic Surgeons and the Journal of Bone & Joint Surgery, and articles published in

AAOS Now. Most guidelines are also distributed at the AAOS Annual Meeting in various

venues such as on Academy Row and at Committee Scientific Exhibits.

Selected guidelines are disseminated by webinar, an Online Module for the Orthopeadic

Knowledge Online website, Radio Media Tours, Media Briefings, and by distributing

them at relevant Continuing Medical Education (CME) courses and at the AAOS

Resource Center.

Other dissemination efforts outside of the AAOS will include submitting the guideline to

the National Guideline Clearinghouse and distributing the guideline at other medical

specialty societies’ meetings.

http://www.aaos.org/research/guidelines/guide.asp


III. ALGORITHMS

This section presents algorithms illustrating the recommendations of the guideline.

Readers are encouraged to use them when reading the document.

Figure 1. Algorithm for Patients with Higher Probability of Hip or Knee

Periprosthetic Joint Infection

Patient at higher probability of

periprosthetic joint infection of the hip

or knee being assessed for infection

ESR/

CRP:

either

positive?

Yes

Infection

Unlikely

No

Nuclear

imaging:

positive?

Yes Infection

Likely

No

2

1

12

Yes

No

Is surgery

planned?

Yes

No

Frozen section

AND/OR

Intra-operative

synovial fluid

white blood cell

count/differential:

positive?

Yes6

43

9

8

7

Aspirate

joint

No

Yes

Repeat

aspiration:

positive?

No

Both Cell

count/differential

AND Culture

positive?

Either cell

count/differential

OR culture

positive?

No

10

Yes

Infection

Likely

5

11

Box 7: Perform repeat aspiration when there is a discrepancy between the probability of infection

and the initial aspiration culture result

Box 9: Perform frozen section when the diagnosis has not been established at the time of surgery;

synovial fluid white blood cell count and differential may also be obtained intra-operatively

Box 10: Nuclear imaging modalities: Labeled leukocyte imaging combined with bone or bone

marrow imaging, FDG-PET imaging, Gallium imaging, or labeled leukocyte imaging


Figure 2. Algorithm for Patients with Lower Probability of Periprosthetic Knee

Infection

Patient at lower probability of

periprosthetic knee infection being

assessed for infection

ESR/

CRP:

either

positive?

Infection

Unlikely

No

YesYes Infection

Likely

No

Is surgery

planned?

Yes

No

Yes

Observe and

Re-evaluate

at 3 months

1

2

6

54

3

9

8

7

Aspirate

joint

No

YesRepeat

aspiration:

positive?

No

Both Cell

count/differential

AND Culture

positive?

Either cell

count/differential

OR culture

positive?

No

10

11

Yes

Frozen section

AND/OR

Intra-operative

synovial fluid

white blood cell

count/differential:

positive?


and the initial aspiration culture result

Box 9: Perform frozen section when the diagnosis has not been established at the time of surgery;

synovial fluid white blood cell count and differential may also be obtained intra-operatively


Figure 3. Algorithm for Patients with Lower Probability of Periprosthetic Hip

Infection with Planned Reoperation

Patient with planned reoperation

at lower probability of periprosthetic

hip infection being assessed for

infection

ESR/

CRP:

either

positive?

Infection

Unlikely

No

YesAspiration (pre-

or intraoperative)

AND/OR

Frozen section:

positive?

Yes Infection

Likely

No

2

1

3

4

5

Box 3: Perform aspiration (pre- or intraoperative) in all patients including synovial fluid white

blood cell count and differential; perform frozen section when the diagnosis has not been

established at the time of surgery.

Figure 4. Algorithm for Patients with Lower Probability of Periprosthetic Hip

Infection without Planned Reoperation

Aspirate

joint

No

Yes Repeat

aspiration:

positive?

Yes

Either

ESR or

CRP

positive?

Yes

No

No

Observe and

Re-evaluate

at 3 months

6

34

Both Cell

count/differential

AND Culture

positive?

Either cell

count/differential

OR culture

positive?

No

Yes

89

Patient without planned reoperation

at lower probability of periprosthetic hip

infection being assessed for infection

1

ESR/

CRP:

both

positive?

2

Infection

Unlikely

5

No

Yes

7

Infection

Likely

5


and the initial aspiration culture result.


IV. RECOMMENDATIONS AND SUPPORTING DATA

RECOMMENDATION 1 In the absence of reliable evidence about risk stratification of patients with a potential

periprosthetic joint infection, it is the opinion of the work group that testing strategies be

planned according to whether there is a higher or lower probability that a patient has a hip

or knee periprosthetic infection.



recommendation based on expert opinion by considering the known potential harm and benefits

associated with the treatment. A Consensus recommendation means that expert opinion supports

the guideline recommendation even though there is no available empirical evidence that meets the

inclusion criteria of the guideline’s systematic review.

Implications: Practitioners should be flexible in deciding whether to follow a recommendation

classified as Consensus, although they may set boundaries on alternatives. Patient preference

should have a substantial influencing role.

Rationale

The diagnosis of periprosthetic infection can be difficult to make and many tests are

available to the clinician. Identification of a periprosthetic joint infection is important, as

subsequent treatment is fundamentally different between cases that have a septic as

opposed to an aseptic mode of failure. Specifically, a missed diagnosis of infection can

lead to a high rate of subsequent failure if specific treatment for the infection is not

considered.

Pre-test probability is weighted heavily in the performance of any diagnostic test. Thus

the identification of a patient as having a higher or lower probability of periprosthetic

joint infection, when initiating the diagnostic evaluation is important. Further, a

determination of how likely or unlikely a diagnosis is, based on patient symptoms, risk

factors, co-morbidities and the physical examination is typically an integral part of the

evaluation that guides clinical decisions. Based on these factors, despite the paucity of

high-level data that supports the specific identification of such factors as they relate to the

probability of periprosthetic joint infection, it is important to outline factors that can

assist the clinician in identifying patients who have a higher probability of periprosthetic

infection and thus warrant a more extensive diagnostic evaluation. Similarly, in patients

who are deemed to have a lower probability of periprosthetic infection, a less vigorous

evaluation may be warranted. Clinicians oftentimes make such assessments of probability

routinely in their practice that leads to more prudent selections among testing modalities

that are based on specific individual patient characteristics. This routine assessment is of

limited cost and low morbidity to the patient.


While the list compiled by the work group is not meant to be exhaustive, several risk

factors were identified as supported by the available evidence as associated with the

presence of periprosthetic joint infection as outlined below. Additional factors, not

supported by the available literature, but unanimously agreed upon by the work group as

additional risk factors to consider were also identified. Finally, several potential risk

factors were identified that the literature did not support as being associated with a

greater probability of periprosthetic infection including smoking status, obesity for

patients who have undergone total knee arthroplasty, the use of drains, and

immunocompromising states for patients who have undergone a total hip arthroplasty.

Analysis of the literature revealed that prolonged post-operative wound drainage and

hematoma formation appeared to increase the likelihood of periprosthetic joint infection

on univariate analysis; however, this was not confirmed by multivariate analysis.

The work group proposes the following table for stratifying patients into higher or lower

probability of infection:

Higher

Probability of

Infection

One or more symptoms, AND at least one or more:

1) risk factor;* OR

2) physical exam finding; OR

3) early implant loosening/osteolysis (as detected by x-

ray)

Lower

Probability of

Infection

Pain or joint stiffness only and none of the following:

1) risk factors;* OR

2) physical exam findings; OR

3) early implant loosening/osteolysis (as detected by x-

ray)

*risk factor supported by evidence or expert opinion

Factors for Risk Stratification

Symptoms Risk Factors Supported

by Evidence

Risk Factors

Supported by

Consensus

Physical

Exam

Findings

Other

1. Pain in

the

replaced

joint

2. Stiffness

in the

replaced

joint

1. Prior infection of the

joint (knee)

2. Superficial surgical

site infection (hip and

knee)

3. Obesity (hip)

4. Extended operative

time (>2.5 hours, hip

and knee)

5. Immunosuppression*

(knee)

1. Any recent (<1yr.)

bacteremia or

candidemia

2. Metachronous

prosthetic joint

infection

3. Skin disorders

(psoriasis, chronic

cellulitis,

lymphedema,

chronic venous

stasis, skin ulcers)

4. IV drug use

5. Recent (<3 yrs.)

1. Warmth,

effusion,

redness,

swelling

2. Sinus

tract

associated

with the

joint

1. Early (<5

yrs.)

implant

loosening

or

osteolysis

(as

detected by

x-ray)


MRSA infection

or colonization

6. Active infection at

other site

Factors not supported as a risk by evidence

1. Smoking

2. Obesity (knee)

3. Use of drains

4. Hematoma or use of anticoagulation (INR>2 or low molecular weight heparins)

5. Immunosuppression* (hip)

*The systematic review considered the following states as indicative of

immunosuppression: HIV, diabetes, hepatitis, chemotherapy or other suppressive

medication such as antimonoclonal antibodies (medications specified in search:

prednisone, infliximab, adalimumab, methotrexate, etanercept), autoimmune diseases

(lupus, rheumatoid arthritis, ankylosing spondylitis, Reiter’s syndrome, psoriatic

arthropathy), inflammatory arthritis, renal disease (chronic renal failure, dialysis), liver

failure, malnourishment, sickle cell disease, hemophilia, solid organ transplant

Supporting Evidence

We included four Level II, two Level III, one Level IV and one Level V prognostic

studies of hip patients (or mixed hip and knee patients with a majority of hip patients).6,

24, 41, 50, 61, 86, 98, 112 We included the lower level studies if they addressed a specific risk

factor that had not been addressed by multiple studies of higher quality. The results of

each study may not be directly comparable with the other studies because the study

authors included different covariates in each model. The results are summarized in Table

5.

We included five Level II, two Level III and one Level IV prognostic studies of knee

patients (or mixed hip and knee patients with a majority of knee patients). 1, 10, 25, 41, 43, 79,

92, 112 We included the lower level studies if they addressed a specific risk factor that had

not been addressed by multiple studies of higher quality. The results of each study may

not be directly comparable with the other studies because the study authors included

different covariates in each model. The results are summarized in Table 6.

We also included thirteen randomized trials investigating the use of drains and one

randomized trial investigating the use of anticoagulation.7, 16, 18, 29, 36, 40, 44, 45, 51, 52, 74, 77, 91,

107 The anticoagulation trial and ten of the drain trials had no periprosthetic infections in

either arm. None of the other three drain trials found a statistically significant difference

in infection rates between groups (see Table 20).

We included seven diagnostic studies for this recommendation. Two studies of other

diagnostic modalities reported data on patients with pain;63, 106

two reported on warmth,

redness, or swelling;63, 102

one reported on sinus tracts;63

and one reported on early

implant failure.57

Two prevalence studies addressed metachronous periprosthetic joint


infection (PJI),62, 72

and one prevalence study addressed recent septicemia.70

With the

exception of the study which reported on early implant failure, the data from these studies

are of low quality and therefore not reliable. The results are summarized in Table 7.

There were no included studies that addressed stiffness, prior MRSA or VRE infection,

skin disorders, IV drug use, or planned revision surgery. We did not include studies on

the prevalence of infection after all revision surgeries because these studies included

patients with revision surgeries planned due to infection. The inclusion of these patients

limits the applicability of these studies.

SUMMARY OF EVIDENCE

Table 5. Results of Prognostic Studies - Hip

Author N

Level of

Evidence Wound D

rain

age

or

Hem

atom

a or

Anti

coag

ula

tion

Exte

nded

Oper

ativ

e T

ime

Pri

or

Infe

ctio

n o

f th

e J

oin

t

Imm

unosu

ppre

ssio

n

Obes

ity

Sm

okin

g

Oth

er S

SI

Use

of

Dra

ins

Oth

er V

aria

ble

(s)

( e

.g., A

ge,

Sex

, et

c.)

Huotari 5614 II x ● x ○ x x x x I

Lubbeke 2495 II x x x x ● x x x I

Smabrekke 28020 II x ● x x x x x x I

Wymenga 2547 II ○ ○ x ○ x x ● x I

Dowsey 1207 III x x x I ● x x x x

Pulido 9245 III ○ ○ x ○ ● x ○ x I

Berbari 924 IV ○ * ○ ○ ○ x ● ○ I

Khan 1767 V x x x x x ○ x x x

* ● = statistically significant, ○ = not significant, x = not studied, I = included as covariate or

matching variable, but data not reported * = extended operative time was studied but the results

were reported by the authors as part of a composite measure.


Table 6. Results of Prognostic Studies - Knee

Author N

Level of

Evidence Wound D

rain

age

or

Hem

atom

a or

Anti

coag

ula

tion

Exte

nded

Op

erat

ive

Tim

e

Pri

or

Infe

ctio

n o

f th

e J

oin

t

Imm

unosu

ppre

ssio

n

Obes

ity

Sm

okin

g

Oth

er S

SI

Use

of

Dra

ins

Oth

er V

aria

ble

(s)

( e

.g., A

ge,

Sex

, et

c.)

Amin 82 II x x x x ○ x x x I

Bordini 9735 II x x x x ○ x x x I

Huotari 4217 II x ● x ○ x x x x I

Jamsen

primary:

38338

revision:

2061

II x ° x ● ● x x x ° x I

Wymenga 345 II ○ ○ x ○ x x ● x I

Dowsey 1214 III x x x ● ● ○ x Z I

Saleh 97 III x x x x x x ● x I

Peersman 349 IV x x x ● ● ● x x I

* ● = statistically significant, ○ = not significant, x = not studied, I = included as covariate or

matching variable, but data not reported, Z = statistically significant protection

° Jamsen study grouped postoperative complications together, including wound hematoma and

wound infections; a postoperative complication was a statistically significant risk factor


Table 7. Summary of Evidence – Diagnostic or Prevalence Studies

Clinical

Indication

Level of

Evidence

Prevalence of Infection

among Patients with

Indication

Positive

Likelihood Ratio

(95% CI)

Negative

Likelihood Ratio

(95% CI)

Early Implant

Loosening I 24%

2.1

(1.36, 3.25)

0.53

(0.29, 0.96)

Pain IV-V 15-51% 1 – 1.18 -

Warmth,

swelling IV 71-100% 2.3 – 2.88 0.82 – 0.92

Sinus Tract IV 100% - 0.86

(0.77, 0.96)

Recent

Septicemia V 45% hematogenous n/a

Metachronous

PJI V 15-19% n/a

*Prevalence based on two studies if range presented, one if a single number

AAOS Clinical Practice Guideline Unit v1.0 062110

21

EXCLUDED ARTICLES

Table 8. Excluded Articles - Recommendation 1

Author Title Reason for Exclusion

Abudu, et al.

2002 The outcome of perioperative wound infection after total hip and knee arthroplasty

Not best available

evidence

Abuzakuk, et al.

2007

Autotransfusion drains in total knee replacement. Are they alternatives to homologous

transfusion?

Does not address

recommendation

Ahlberg, et al.

1981 Secondary operations after knee joint replacement

Not best available

evidence

Ainscow, et al.

1984 The risk of haematogenous infection in total joint replacements

Not best available

evidence

Amin, et al.

2006

Does obesity influence the clinical outcome at five years following total knee replacement

for osteoarthritis?

Not best available

evidence

Amin, et al.

2008

A prospective randomised controlled trial of autologous retransfusion in total knee

replacement

Does not address

recommendation

Andrew, et al.

2008 Obesity in total hip replacement

Not best available

evidence

Andrews, et al.

1981 Deep infection after total hip replacement

Not best available

evidence

Asensio, et al.

2005

Preoperative low molecular weight heparin as venous thromboembolism prophylaxis in

patients at risk for prosthetic infection after knee arthroplasty

Not best available

evidence

Bahebeck, et al.

2009

Implant orthopaedic surgery in HIV asymptomatic carriers: Management and early

outcome

<25 arthroplasty

patients per group

Bedi, et al.

1997 An audit of early hospital readmission after primary knee joint replacement <25 patients/arm

Bengtson, et al.

1991 The infected knee arthroplasty. A 6-year follow-up of 357 cases

Not best available

evidence


22

Table 8. Excluded Articles (Continued)


Beyer, et al.

1991 Primary total knee arthroplasty in patients with psoriasis

Not best available

evidence

Bohm, et al.

1998

Is there a future for hinged prostheses in primary total knee arthroplasty? A 20-year

survivorship analysis of the Blauth prosthesis

Not best available

evidence

Bong, et al.

2004 Stiffness after total knee arthroplasty

Narrative review,

bibliography screened

Bongartz, et al.

2008

Incidence and risk factors of prosthetic joint infection after total hip or knee replacement in

patients with rheumatoid arthritis

Not best available

evidence

Bosch, et al.

1980 An analysis of 119 loosenings in total hip endoprostheses Insufficient Data

Bourne, et al.

1994

Pain in the thigh following total hip replacement with a porous-coated anatomic prosthesis

for osteoarthrosis. A five-year follow-up study

Does not address

recommendation

Brander, et al.

2003 Predicting Total Knee Replacement Pain: A Prospective, Observational Study

Does not address

recommendation

Byrne, et al.

2007 Outcome following deep wound contamination in cemented arthroplasty

Not best available

evidence

Cameron,

1993 Knee effusion after total knee replacement

Narrative review,


Carlsson,

1981 351 total hip replacements according to Charnley. A review of complications and function

Not best available

evidence

Chan, et al.

1996 Obesity and quality of life after primary hip arthroplasty

Does not address

recommendation

Charnley,

1972

Postoperative infection after total hip replacement with special reference to air

contamination in the operating room

Not best available

evidence


23



Cherney, et al.

1983 Total hip replacement in the previously septic hip No comparison group

Chesney, et al.

2008 Infection after knee arthroplasty a prospective study of 1509 cases

Not best available

evidence

Choong, et al.

2007

Risk factors associated with acute hip prosthetic joint infections and outcome of treatment

with a rifampinbased regimen

Not best available

evidence

Clements, et al.

2007

Risk stratification for surgical site infections in Australia: evaluation of the US National

Nosocomial Infection Surveillance risk index

Not relevant - not

specific to pji

Dennis,

2004 Evaluation of painful total knee arthroplasty

Narrative review,


Deshmukh, et al.

2002 Does body weight influence outcome after total knee arthroplasty? A 1-year analysis

Not relevant - not

specific to pji

Dowsey, et al.

2008

Early outcomes and complications following joint arthroplasty in obese patients: a review

of the published reports

Systematic review,


Dowsey, et al.

2008 Obesity is a major risk factor for prosthetic infection after primary hip arthroplasty

Not best available

evidence

Drancourt, et al.

1997 Psoriasis is a risk factor for hip-prosthesis infection <25 patients

Drinkwater, et al.

1995 Optimal timing of wound drain removal following total joint arthroplasty

Does not address

recommendation

Duffy, et al.

2005 Evaluation of patients with pain following total hip replacement

Narrative review,


Duffy, et al.

2006 Evaluation of patients with pain following total hip replacement

Narrative review,



24



Ehrenkranz,

1981

Surgical wound infection occurrence in clean operations; risk stratification for interhospital

comparisons

Not relevant - not

specific to pji

Espehaug, et al.

1997

Patient-related risk factors for early revision of total hip replacements. A population

register-based case-control study of 674 revised hips

Not best available

evidence

Fan, et al.

2008 Infection in primary total knee replacement Insufficient Data

Fernandez, et al.

1997 Risk infection factors in the total hip replacement

Not relevant - no

relevant risk factors

investigated

Fitzgerald, et al.

1977 Deep wound sepsis following total hip arthroplasty

Not best available

evidence

Foldes, et al.

1992 Ultrasonography after hip arthroplasty <25 patients/arm

Foran, et al.

2004 The outcome of total knee arthroplasty in obese patients

Not best available

evidence

Foran, et al.

2004 Total knee arthroplasty in obese patients: a comparison with a matched control group

Not best available

evidence

Gaine, et al.

2000 Wound infection in hip and knee arthroplasty

Not relevant - not

specific to pji

Galat, et al.

2008

Early return to surgery for evacuation of a postoperative hematoma after primary total

knee arthroplasty

Not best available

evidence

Galat, et al.

2009 Surgical treatment of early wound complications following primary total knee arthroplasty

Not relevant - not

specific to pji

Garibaldi, et al.

1991 Risk factors for postoperative infection

Not relevant - not

specific to pji


25



Gonzalez, et al.

2004 The failed total knee arthroplasty: evaluation and etiology

Narrative review,


Gordon, et al.

1990 Risk factors for wound infections after total knee arthroplasty

Not best available

evidence

Grant, et al.

2008

Two-year outcomes in primary THA in obese male veterans administration medical center

patients

Not relevant - not

specific to pji

Greene, et al.

1991

Preoperative nutritional status of total joint patients. Relationship to postoperative wound

complications

Not best available

evidence

Hamilton, et al.

2008 Deep infection in total hip arthroplasty

Not best available

evidence

Horberg, et al.

2006

Surgical outcomes in human immunodeficiency virus-infected patients in the era of highly

active antiretroviral therapy

Not relevant - not

specific to pji

Horne, et al.

2008

The influence of steroid injections on the incidence of infection following total knee

arthroplasty

Not relevant - not

specific to pji

Ibrahim, et al.

2005 No influence of body mass index on early outcome following total hip arthroplasty

Not best available

evidence

Ilstrup, et al.

1973 Factors influencing the results in 2,012 total hip arthroplasties Insufficient Data

Jaberi, et al.

2008

Procrastination of wound drainage and malnutrition affect the outcome of joint

arthroplasty

Does not address

recommendation

Jacobsen, et al.

1980

Prophylactic coverage of dental patients with artificial joints: a retrospective analysis of

thirty-three infections in hip prostheses

Does not address

recommendation

Jacobson, et al.

1986 Dental treatment and late prosthetic joint infections

Does not address

recommendation


26



Jain, et al.

2005 Comorbidities increase complication rates in patients having arthroplasty

Not relevant - not

specific to pji

James, et al.

1982 Total hip revision arthroplasty: does sepsis influence the results?

Narrative review,


Jensen, et al.

1982 Nutrition in orthopaedic surgery Insufficient Data

Jerry, et al.

1988 Old sepsis prior to total knee arthroplasty No comparison group

Jibodh, et al.

2004 In-hospital outcome and resource use in hip arthroplasty: Influence of body mass

Not best available

evidence

Jiganti, et al.

1993

A comparison of the perioperative morbidity in total joint arthroplasty in the obese and

nonobese patient

Not best available

evidence

Johnson, et al.

1986 The outcome of infected arthroplasty of the knee

Not best available

evidence

Jones, et al.

1979 GUEPAR knee arthroplasty results and late complications

Not best available

evidence

Jupiter, et al.

1981 Total hip arthroplasty in the treatment of adult hips with current or quiescent sepsis No comparison group

Kaspar, et al.

2005 Infection in hip arthroplasty after previous injection of steroid

Not best available

evidence

Kessler, et al.

2003 Influence of operation duration on perioperative morbidity in revision total hip arthroplasty

Not relevant - not

specific to pji

Khuri, et al.

1995

The National Veterans Administration Surgical Risk Study: risk adjustment for the

comparative assessment of the quality of surgical care

Not relevant - not

specific to pji


27



Kim,

1991 Total arthroplasty of the hip after childhood sepsis No comparison group

Kim, et al.

2003 Total hip arthroplasty in adult patients who had childhood infection of the hip No comparison group

Kim, et al.

2006 Clinical impact of obesity on stability following revision total hip arthroplasty Insufficient Data

Kim, et al.

2004

Stiffness after total knee arthroplasty. Prevalence of the complication and outcomes of

revision

Does not address

recommendation

Knobben, et al.

2006 Intraoperative contamination influences wound discharge and periprosthetic infection

Not best available

evidence

Knutson, et al.

1986 Survival of knee arthroplasties. A nation-wide multicentre investigation of 8000 cases

Not best available

evidence

Lai, et al.

2007

Presence of medical comorbidities in patients with infected primary hip or knee

arthroplasties

Not best available

evidence

Lawton, et al.

1999

The use of heparin in patients in whom a pulmonary embolism is suspected after total hip

arthroplasty

Not best available

evidence

Lazzarini, et al.

2001 Postoperative infections following total knee replacement: an epidemiological study

Not best available

evidence

Leong, et al.

2006

Duration of operation as a risk factor for surgical site infection: comparison of English and

US data

Not relevant - not

specific to pji

Lonner, et al.

1999 Prodromes of failure in total knee arthroplasty

Does not address

recommendation

Lubbeke, et al.

2008 Outcomes of obese and nonobese patients undergoing revision total hip arthroplasty

Not best available

evidence


28



Mac, et al.

1993

Comparison of autoreinfusion and standard drainage systems in total joint arthroplasty

patients

Does not address

recommendation

Malinzak, et al.

2009

Morbidly Obese, Diabetic, Younger, and Unilateral Joint Arthroplasty Patients Have

Elevated Total Joint Arthroplasty Infection Rates

Not best available

evidence

Mandalia, et al.

2008 Evaluation of patients with a painful total knee replacement

Narrative review,


Marchant, et al.

2009

The impact of glycemic control and diabetes mellitus on perioperative outcomes after total

joint arthroplasty

Not relevant - not

specific to pji

McDonald, et al.

1989 Two-stage reconstruction of a total hip arthroplasty because of infection No comparison group

McLaughlin, et al.

2006 The outcome of total hip replacement in obese and non-obese patients at 10- to 18-years

Not best available

evidence

Meding, et al.

2003 Total Knee Replacement in Patients with Diabetes Mellitus

Not best available

evidence

Menon, et al.

1983 Charnley low-friction arthroplasty in patients with psoriasis

Not best available

evidence

Minnema, et al.

2004 Risk factors for surgical-site infection following primary total knee arthroplasty

Not relevant - not

specific to pji

Mont, et al.

1996

Cementless total knee arthroplasty in obese patients: A comparison with a matched control

group

Not relevant - not

specific to pji

Moran, et al.

2005 Does body mass index affect the early outcome of primary total hip arthroplasty? Insufficient Data

Muilwijk, et al.

2006

Random effect modelling of patient-related risk factors in orthopaedic procedures: results

from the Dutch nosocomial infection surveillance network 'PREZIES'

Not best available

evidence


29



Mulhall, et al.

2006 Current etiologies and modes of failure in total knee arthroplasty revision

Not best available

evidence

Mulier, et al.

1973 Postoperative infection in total hip replacement

Not best available

evidence

Murphy, et al.

1993 The effectiveness of suction drainage in total hip arthroplasty <25 patients/arm

Murray,

1973 Results in patients with total hip replacement arthroplasty Insufficient Data

Namba, et al.

2005 Obesity and perioperative morbidity in total hip and total knee arthroplasty patients

Not best available

evidence

Nelson, et al.

2005 Stiffness after total knee arthroplasty. Surgical technique

Does not address

recommendation

Niki, et al.

2006

Phenotypic characteristics of joint fluid cells from patients with continuous joint effusion

after total knee arthroplasty

Not best available

evidence

Niki, et al.

2007 Five types of inflammatory arthritis following total knee arthroplasty

Not best available

evidence

Ong, et al.

2009 Prosthetic Joint Infection Risk After Total Hip Arthroplasty in the Medicare Population

Not best available

evidence

Papagelopoulos, et al.

1996

Long term outcome and survivorship analysis of primary total knee arthroplasty in patients

with diabetes mellitus

Not best available

evidence

Parker, et al.

2004 Closed suction drainage for hip and knee arthroplasty: a meta-analysis

Systematic review,


Parker, et al.

2007 Closed suction surgical wound drainage after orthopaedic surgery

Systematic review,



30



Parratte, et al.

2008 The Stiff Total Knee Arthroplasty: A Contemporary Approach

Narrative review,


Partanen, et al.

2006 Impact of deep infection after hip fracture surgery on function and mortality

Not relevant - not

specific to pji

Partio, et al.

1994 Survival of the Townley knee. 360 cases with 8 (0.1-15) years' follow-up

Not best available

evidence

Parvizi, et al.

2007 Does 'excessive' anticoagulation predispose to periprosthetic infection?

Not best available

evidence

Parvizi, et al.

2006 Management of stiffness following total knee arthroplasty

Does not address

recommendation

Pasticci, et al.

2007

Prosthetic infections following total knee arthroplasty: A six-year prospective study (1997-

2002)

Does not address

recommendation

Patel, et al.

2007

Factors associated with prolonged wound drainage after primary total hip and knee

arthroplasty

Not relevant - not

specific to pji

Peersman, et al.

2006

Prolonged operative time correlates with increased infection rate after total knee

arthroplasty

Not best available

evidence

Peersman, et al.

2008

ASA physical status classification is not a good predictor of infection for total knee

replacement and is influenced by the presence of comorbidities Duplicate data

Perka, et al.

2000

The influence of obesity on perioperative morbidity and mortality in revision total hip

arthroplasty

Not best available

evidence

Petty, et al.

1975 Infection after total knee arthroplasty

Not best available

evidence

Pons, et al.

1999 Infected total hip arthroplasty--the value of intraoperative histology Composite measure


31



Poss, et al.

1984

Factors influencing the incidence and outcome of infection following total joint

arthroplasty

Not best available

evidence

Pritchett, et al.

1991 Knee replacement in morbidly obese women

Not best available

evidence

Ragni, et al.

1995

Postoperative infection following orthopaedic surgery in human immunodeficiency virus-

infected hemophiliacs with CD4 counts (less-than or equal to) 200/mm(3)

Not best available

evidence

Ridgeway, et al.

2005 Infection of the surgical site after arthroplasty of the hip

Not relevant - not

specific to pji

Robbins, et al.

2002

Evaluation of pain in patients with apparently solidly fixed total hip arthroplasty

components

Narrative review,


Rodriguez-Merchan,

2007 Total knee replacement in haemophilic arthropathy

Not best available

evidence

Sachs, et al.

2003

Does anticoagulation do more harm than good?: A comparison of patients treated without

prophylaxis and patients treated with low-dose warfarin after total knee arthroplasty

Not best available

evidence

Sadr, et al.

2006

The impact of tobacco use and body mass index on the length of stay in hospital and the

risk of post-operative complications among patients undergoing total hip replacement

Not relevant - not

specific to pji

Schmalzried, et al.

1992

Etiology of deep sepsis in total hip arthroplasty. The significance of hematogenous and

recurrent infections

Not best available

evidence

Scuderi,

2005 The stiff total knee arthroplasty: Causality and solution

Narrative review,


Serna, et al.

1994 Total knee arthroplasty in diabetic patients. Comparison to a matched control group

Not best available

evidence

Shih, et al.

2004 Total knee arthroplasty in patients with liver cirrhosis

Not best available

evidence


32



Shrader, et al.

2003 Primary TKA in Patients with Lymphedema

Not best available

evidence

Silva, et al.

2005 Long-term results of primary total knee replacement in patients with hemophilia

Not best available

evidence

Solomon, et al.

2006

Development of a preliminary index that predicts adverse events after total knee

replacement

Does not address

recommendation

Spicer, et al.

2001 Body mass index as a predictor of outcome in total knee replacement

Not best available

evidence

Stern, et al.

1989 Total knee arthroplasty in patients with psoriasis <25 patients

Stern, et al.

1990 Total knee arthroplasty in obese patients

Does not address

recommendation

Surin, et al.

1983 Infection after total hip replacement. With special reference to a discharge from the wound

Not best available

evidence

Tannenbaum, et al.

1997 Infection around joint replacements in patients who have a renal or liver transplantation <25 patients

van Loon, et al.

2000 The kinematic total knee arthroplasty. A 10- to 15-year follow-up and survival analysis

Not best available

evidence

Vannini, et al.

1984 Diabetes as pro-infective risk factor in total hip replacement

Not best available

evidence

Varley, et al.

1995

Wound drains in proximal femoral fracture surgery: a randomized prospective trial of 177

patients

Not relevant - not

specific to pji

Waldman, et al.

1997 Total knee arthroplasty infections associated with dental procedures

Does not address

recommendation


33



Wang,

1984 Clinical observations on Blauth's total endoprosthesis of the knee joint Insufficient Data

Weiss, et al.

1993 Persistent wound drainage after primary total knee arthroplasty <25 patients

Went, et al.

1995 Recurrence of infection after revision of infected hip arthroplasties No comparison group

White, et al.

1990 Early morbidity after total hip replacement: rheumatoid arthritis versus osteoarthritis

Not relevant - not

specific to pji

Wilson, et al.

1990

Infection as a complication of total knee-replacement arthroplasty. Risk factors and

treatment in sixty-seven cases

Not best available

evidence

Winiarsky, et al.

1998 Total knee arthroplasty in morbidly obese patients

Not best available

evidence

Yasunaga, et al.

2009

Analysis of factors affecting operating time, postoperative complications, and length of

stay for total knee arthroplasty: Nationwide web-based survey

Not relevant - not

specific to pji

Yasunaga, et al.

2009

High-volume surgeons in regard to reductions in operating time, blood loss, and

postoperative complications for total hip arthroplasty

Not relevant - not

specific to pji

Yong, et al.

2001 Risk factors for infection in total hip replacement surgery at Hospital Kuala Lumpur

Not relevant - not

specific to pji

Zamora-Navas, et al.

1999

Closed suction drainage after knee arthroplasty. A prospective study of the effectiveness of

the operation and of bacterial contamination <25 patients per group


34

STUDY QUALITY

Table 9. Quality of Diagnostic Studies

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed

Author N Index Test Level of

Evidence

Lachiewicz 142 Implant in situ <5

years I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Teller 161

Local signs

(erythema,

warmth, edema)

IV ○ ● ● ● ● ● ● ● ● ● ? ● ● ●

Magnuson 98 Warmth IV ○ ● ● ● ● ● ● ● ? ● ? ● ● ●

Magnuson 98 Swelling or

erythema IV ○ ● ● ● ● ● ● ● ? ● ? ● ● ●

Magnuson 98 Sinus tract IV ○ ● ● ● ● ● ● ● ? ● ? ● ● ●

Magnuson 98 Pain IV ○ ● ● ● ● ● ● ● ? ● ? ● ● ●

Virolainen 68 Pain V ? ○ ● ● ● ● ● ● ● ? ● ● ● ●


35

Table 10. Quality of Prognostic Studies

● = Yes

○ = No

? = Not Reported

n/a = Not Applicable

pro

spec

tive

var

iable

s id

enti

fied

in M

ethods

all

var

iable

s dis

cuss

ed i

n r

esult

s

suff

icie

nt

pat

ients

per

var

iable

(10)

suff

icie

nt

even

ts p

er v

aria

ble

(10)

unam

big

uous

codin

g

coll

inea

rity

tes

ted o

r not

rele

van

t

fitt

ing p

roce

dure

sta

ted

goodnes

s of

fit

stat

s re

port

ed

mod

el v

alid

atio

n

Author Risk Factor N Joint Level of Evidence

Wymenga Hematoma 2547 Hip II ● ○ ? ● ○ ● ○ ● ○ ○

Wymenga Hematoma 345 Knee II ● ○ ? ● ○ ● ○ ● ○ ○

Pulido Hematoma/ wound drainage 9245 Mixed III ○ ● ● ● ○ ● ○ ● ○ ○

Smabrekke Operating time 28020 Hip II ● ● ○ ● ● ● ● ● ○ ○

Huotari Operating time 5614 Hip II ● ● ● ● ○ ● ○ ● ○ ○

Huotari Operating time 4217 Knee II ● ● ● ● ○ ● ○ ● ○ ○

Wymenga Operating time 2547 Hip II ● ○ ? ● ○ ● ○ ● ○ ○

Wymenga Operating time 345 Knee II ● ○ ? ● ○ ● ○ ● ○ ○

Jamsen Prior infection 819 Knee II Multiple Regression of Joint Registry Data

(see below for registry quality)

Berbari Prior joint infection 924 Mixed IV (case-control) ○ ○ ● ● ● ● ● ● ○ ●

Huotari Rheumatoid arthritis 5614 Hip II ● ● ● ● ○ ● ○ ● ○ ○


36

Table 10. Quality of Prognostic Studies (Continued)

● = Yes

○ = No

? = Not Reported


pro

spec

tive

var

iable

s id

enti

fied

in M

ethods

all

var

iable

s dis

cuss

ed i

n r

esult

s

suff

icie

nt

pat

ients

per

var

iable

(10)

suff

icie

nt

even

ts p

er v

aria

ble

(10)

unam

big

uous

codin

g

coll

inea

rity

tes

ted o

r not

rele

van

t

fitt

ing p

roce

dure

sta

ted

goodnes

s of

fit

stat

s re

port

ed

model

val

idat

ion


Huotari Rheumatoid arthritis 4217 Knee II ● ● ● ● ○ ● ○ ● ○ ○

Wymenga Diabetes 2547 Hip II ● ○ ? ● ○ ● ○ ● ○ ○

Wymenga Use of steroids 2547 Hip II ● ○ ? ● ○ ● ○ ● ○ ○

Wymenga Diabetes 345 Knee II ● ○ ? ● ○ ● ○ ● ○ ○

Wymenga Use of steroids 345 Knee II ● ○ ? ● ○ ● ○ ● ○ ○

Jamsen Rheumatoid arthritis primary: 38338

revision: 2061 Knee II

Multiple Regression of Joint Registry Data


Lubbeke Obesity

(BMI ≥30) 2495 Hip II ● ● ● ● ○ ● ● ● ○ ○

Dowsey Obesity 1207 Hip III ○ ● ● ● ● ● ● ● ○ ○

Amin Obesity 82 Knee II ● ● ● n/a ○ ● ● ● ○ ○

Bordini Obesity 9735 Knee II Multiple Regression of Joint Registry Data



37

Table 10. Quality of Prognostic Studies (Continued)

● = Yes

○ = No

? = Not Reported


pro

spec

tive

var

iable

s id

enti

fied

in M

ethods

all

var

iable

s dis

cuss

ed i

n r

esult

s

suff

icie

nt

pat

ients

per

var

iable

(10)

suff

icie

nt

even

ts p

er v

aria

ble

(10)

unam

big

uous

codin

g

coll

inea

rity

tes

ted o

r not

rele

van

t

fitt

ing p

roce

dure

sta

ted

goodnes

s of

fit

stat

s re

port

ed

model

val

idat

ion


Pulido Obesity

(BMI >40) 9245 Mixed III ○ ● ● ● ○ ● ○ ● ○ ○

Dowsey Smoking 1214 Knee III ○ ● ● ● ○ ● ○ ○ ○ ○

Peersman Smoking 349 Knee IV (case-contol) ○ ○ ○ ? ? ● ● ● ● ○

Khan Smoking 1767 Hip V (univariate) ● n/a n/a n/a n/a n/a n/a n/a n/a n/a

Wymenga Wound infection 2547 Hip II ● ○ ? ● ○ ● ○ ● ○ ○

Wymenga Wound infection 345 Knee II ● ○ ? ● ○ ● ○ ● ○ ○

Pulido Wound infection 9245 Mixed III ○ ● ● ● ○ ● ○ ● ○ ○

Saleh Surgical site infection 97 Mixed III ○ ● ● n/a ○ ● ● ● ○ ○


38

Table 11. Risk Factors - Quality of Joint Registries

● = Yes ○ = No ? = Not Reported

Man

dat

ory

Dat

a

Subm

issi

on

Popula

tion

-Bas

ed R

egis

try

Val

idat

ed D

ata

>90%

of

pat

ients

cap

ture

d

Sta

tist

ical

Qual

ity C

ontr

ol

Mea

sure

s P

erfo

rmed

Ensu

res

corr

ect

dia

gnosi

s

Author Risk Factor N Joint Level of

Evidence

Jamsen

Prior infection

(reason for revision

was infection)

819 Knee II ● ● ○ ● ? ●

Jamsen Rheumatoid arthritis primary: 38338

revision: 2061 Knee II ● ● ○ ● ? ●

Bordini Obesity 9735 Knee II ● ● ? ● ? ●


39

Table 12. Risk Factors - Quality of Randomized Trials

● = Yes ○ = No ? = Not Reported

Sto

chas

tic

Ran

dom

izat

ion

All

oca

tion C

once

alm

ent

Subje

cts

Bli

nd

Ass

esso

r B

lind

>80%

Foll

ow

-Up

Sim

ilar

in O

utc

om

e at

Bas

elin

e

Author Treatment Control N Level of

Evidence

Confalonieri Drain No Drain 78 II ? ● ○ ○ ● ●

Crevoisier Drain No Drain 98 II ? ● ○ ○ ● ●

Esler Drain No Drain 100 II ? ● ○ ○ ● ●

Gonzalez Della

Valle Drain No Drain 104 II

● ○ ○ ○ ● ●

Holt Drain No Drain 137 II ○ ○ ○ ○ ● ●

Jenny Drain No Drain 60 II ? ● ○ ○ ● ●

Johansson Drain No Drain 105 II ? ● ○ ○ ● ●

Kim Drain No Drain 138 II ● ● ○ ○ ● ●

Kim Drain No Drain 96 II ● ● ○ ○ ● ●

Niskanen Drain No Drain 97 II ? ○ ○ ○ ● ●

Ovadia Drain No Drain 88 II ? ● ○ ○ ● ●

Ritter Drain No Drain 415 II ? ○ ○ ○ ● ●

Walmsley Drain No Drain 577 II ? ● ○ ○ ● ●

Bergqvist Thromboprophylaxis No

Thromboprophylaxis 161 II ? ○ ○ ○ ● ●


40

STUDY RESULTS

Table 13. Pain as a Predictor of Periprosthetic Infection

Level of

Evidence Author N Test

Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity

(95% CI) TP FP FN TN

IV Magnuson 98 Pain

Intraoperative

Cultures or

Histology

Mixed 1 - 1

(0.93, 1)

0

(0, .07) 50 48 0 0

V Virolainen 68 Pain Intraoperative

Cultures Mixed

1.18

(1.06, 1.31) 0

1

(0.66, 1)

.15

(.07, .27) 9 50 0 9

Table 14. Warmth, Erythema, Swelling as Predictors of Periprosthetic Infection

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


IV Magnuson 98 Warmth

Intraoperative

Cultures or

Histology

Mixed 2.88

(0.61, 13.6)

0.92

(0.82, 1.03)

0.12

(0.05,

0.24)

0.96

(0.86,

0.99)

6 2 44 46

IV Magnuson 98

Swelling

or

Erythema

Intraoperative

Cultures or

Histology

Mixed 2.3

(0.88, 6.05)

0.85

(0.71, 1.02)

0.24

(0.13,

0.38)

0.90

(0.77,

0.97)

12 5 38 43

IV Teller 161

Local

Signs

(erythema,

warmth,

edema)

Intraoperative

Cultures or

Frank

Purulence

Mixed - 0.82

(0.67, 0.99)

0.18

(0.05,

0.40)

1

(0.97, 1) 4 0 18 139


41

Table 15. Early Implant Failure as a Predictor of Periprosthetic Infection

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Lachiewicz 142

Implant

in situ

<5 years

Intraoperative

Cultures or

Gross

Purulence

Hip 2.1

(1.36, 3.25)

0.53

(0.29, 0.96)

0.63

(0.38, 0.84)

0.70

(0.61, 0.78) 12 37 7 86

Table 16. Sinus Tract as a Predictor of Periprosthetic Infection

Level of

Evidence Author Risk Factor Joint N Results

IV Magnuson sinus tract Mixed 98 OR undefined - all 7 with sinus

tract had infection (p=.01)

Table 17. Prevalence of Periprosthetic Infection among Patients with Bacteremia

Level of

Evidence Author Risk Factor N Infections %

V Murdoch S. aureus bacteremia 53 24 hematogenous,

9 primary

45% hematogenous,

62% overall


42

Table 18. Prevalence of Periprosthetic Infection among Patients with Metachronous Periprosthetic Infection

Level of

Evidence Author Risk Factor N Infections %

V Luessenhop Metachronous PJI 145 27 19%

V Murray Metachronous PJI 68 10 15%

Table 19. Anticoagulation RCT

Level of

Evidence Author Risk Factor Joint N Results

II Bergqvist Anticoagulation Hip 161 -

(RCT with no infections)


43

Table 20. Use of Drains RCTs

Level of

Evidence Author Risk Factor Joint N

Results

Odds Ratio (95% CI)

II Esler Drains Knee 100 0 (0, 39)

II Kim Drains Knee 138 0 (0, 5.3)

II Walmsley Drains Hip 577 1.05 (.08, 14.5)

II Confalonieri Drains Knee 78 -

(no infections)

II Crevoisier Drains Mixed 98 -

(no infections)

II Gonzalez

Della Valle Drains Hip 104

-

(no infections)

II Holt Drains Knee 137 -

(no infections)

II Jenny Drains Knee 60 -

(no infections)

II Johansson Drains Hip 105 -

(no infections)

II Kim Drains Hip 96 -

(no infections)

II Niskanen Drains Mixed 97 -

(no infections)

II Ovadia Drains Mixed 88 -

(no infections)

II Ritter Drains Mixed 415 -

(no infections)


44

RECOMMENDATION 2 We recommend erythrocyte sedimentation rate and C-reactive protein testing for patients

assessed for periprosthetic joint infection.


Description: Evidence is based on two or more “High” strength studies with consistent findings

for recommending for or against the intervention. A Strong recommendation means that the

benefits of the recommended approach clearly exceed the potential harm (or that the potential

harm clearly exceeds the benefits in the case of a strong negative recommendation), and that the

strength of the supporting evidence is high.

Implications: Practitioners should follow a Strong recommendation unless a clear and compelling


Rationale

Six Level I studies evaluating the ESR,11, 21, 37, 48, 93, 96

six Level I studies evaluating the

CRP,11, 21, 31, 37, 93, 96

and two Level I studies evaluating the combined use of ESR and

CRP 37, 96

were used for analysis.

The use of screening inflammatory markers (ESR and CRP) is the starting point in the

work-up investigations for the diagnosis or exclusion of periprosthetic joint infection.

Our systematic review of the literature found strong evidence for using both ESR and

CRP testing. We recommend use of this combination of tests to “rule out” infection.

The combined use of ESR and CRP is a very good “rule out” test. When both the ESR

and CRP are negative, periprosthetic infection is unlikely (negative likelihood ratio 0 –

0.06). When both tests are positive, periprosthetic infection must be considered (positive

likelihood ratio 4.3 – 12.1), and this result warrants further investigations. However, the

clinician also needs to be aware of other inflammatory conditions such as rheumatoid

arthritis, neoplasms, coronary artery disease, polymyalgia rheumatica, inflammatory

bowel disease, etc. that can lead to elevation of inflammatory markers. The use of either

test alone is less reliable for either ‘ruling out’ or ‘ruling in’ infection than when both

tests are combined. A negative ESR is better at ‘ruling out’ infection than a positive

result is for ‘ruling in’ infection (better negative likelihood ratio than positive likelihood

ratio). Similarly, the CRP is a better test for ‘ruling out’ infection, but somewhat better

than the ESR at ‘ruling in’ infection.

The evidence strongly supports obtaining an ESR and CRP in all patients being assessed

for periprosthetic infection.

Supporting Evidence

The systematic review for this recommendation included studies investigating the

diagnostic utility of not only ESR and CRP, but also radiographs and peripheral white

blood cell counts. With the exception of two studies that investigated the joint use of ESR


45

and CRP, 37, 96

there are no data looking at the use of a combination of these tests. The

available data are from studies that investigated each test in isolation.

For erythrocyte sedimentation rates, we included three studies of hip patients, two of

knee patients, and one of mixed hip and knee patients. 11, 21, 37, 48, 93, 96

All studies

produced reliable data. Meta-analysis of all ESR studies indicated that threshold effects

may be responsible for much of the differences between studies. Using a threshold of 30

mm/hr, a positive result produced a small (but sometimes important) change in the

probability of infection, while a negative result produced a moderate change (see Figure

5).

For C-reactive protein, we included two studies of hip patients, three of knee patients,

and one of mixed hip and knee patients. 11, 21, 31, 37, 93, 96

All studies produced reliable data.

Meta-analysis of all CRP studies indicated significant between-study heterogeneity (I2

=83%), and adjusting for differences in thresholds did not explain the variation between

studies. With the exception of one study with wide confidence intervals,93

the positive

and negative likelihood ratios were statistically significant (see Table 25).

We included two studies with reliable data that looked at using a combination of ESR and

CRP to diagnose infection.37, 96

A negative result on both tests was very good at ruling

out infection. A positive result on one of the tests produced a small (likelihood ratio <5)

change in probability, so it was not very good at ruling in infection. A positive result on

both tests was a better “rule in” test (see Table 26).

For radiographs, we included one study of hip patients with reliable data,19

one study of

hip patients with moderately reliable data,9 and one study of knee patients with

moderately reliable data.5 There was no consistent evidence of statistically significant

diagnostic benefit (see Table 27) however, findings such as periostitis or early osteolysis

may indicate infection. In addition, radiographs can provide alternative explanations for

joint pain or dysfunction and are routinely obtained in the evaluation of the painful or

failed hip or knee arthroplasty.

For peripheral white blood cell counts, we included three studies of hip patients and one

of mixed hip and knee patients with reliable data.11, 83, 93, 99

We included three additional

studies of mixed hip and knee patients with moderately reliable data.8, 23, 105

The

thresholds differed in each study. Meta-analysis of all peripheral white blood cell count

studies indicated significant between-study heterogeneity (I2

=98%), and adjusting for

differences in thresholds did not explain the variation between studies. With the

exception of one study with wide confidence intervals,93

the positive and negative

likelihood ratios were statistically significant (see Table 28).


46

SUMMARY OF EVIDENCE

Table 21. Radiography and Serology Summary of Evidence

Test

Number

of

Studies

Positive

Likelihood Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity

(95% CI)

ESR – meta-

analysis

(I2=26%)

6 2.9

(1.7, 4.8)

0.15

(0.09, 0.27)

0.90

(0.82, 0.94)

0.69

(0.51, .82)

CRP (range) 6 2.4 – 27.1 0.05 – 0.8 0.30 – 0.95 0.71 – 0.96

ESR and CRP -

positive if both

positive (range)

2 4.34 – 12.1 0.14 - 0.21 0.80 – 0.89 0.79 – 0.93

ESR and CRP -

positive if one

positive (range)

2 1.74 – 4.22 0 – 0.06 0.96 - 1 0.43 – 0.77

Radiograph –

lucency (range) 2 1.2 – 2.99 0.55 – 0.95 0.25 – 0.55 0.79 – 0.82

Radiograph –

periostitis

(range)

2 1.04 – 20.8 0.82 - 0.92 0.17 – 0.70 0.33 - 1

Radiograph –

other measures

(range)

3 0.52 – 2.4 0.3 - 1.23 0.17 – 0.80 0.67 – 0.84

WBC (range) 7 1.77 – 8.45 0.08 – 0.89 0.10 – 0.94 0.60 -1

*Range presented when fewer than four studies or when meta-analysis indicated heterogeneity


47

EXCLUDED ARTICLES



Austin, et al.

2008 A simple, cost-effective screening protocol to rule out periprosthetic infection

Not best available

evidence

Bare, et al.

2006 Preoperative evaluations in revision total knee arthroplasty

Not best available

evidence

Bergstrom, et al.

1974

Radiographic abnormalities caused by postoperative infection following total hip

arthroplasty <25 patients/arm

Canner, et al.

1984 The infected hip after total hip arthroplasty

Not relevant - not

diagnostic study

Carlsson, et al.

1978 Erythrocyte sedimentation rate in infected and non-infected total-hip arthroplasties <25 patients/arm

Chevillotte, et al.

2008 Inflammatory Laboratory Markers in Periprosthetic Hip Fractures

Not best available

evidence

Choudhry, et al.

1992 Plasma viscosity and C-reactive protein after total hip and knee arthroplasty

Not relevant - not

diagnostic study

Chryssikos, et al.

2008 FDG-PET imaging can diagnose periprosthetic infection of the hip

Not best available

evidence

Covey, et al.

1987 Clinical significance of the erythrocyte sedimentation rate in orthopaedic surgery

Narrative review,


Duff, et al.

1996 Aspiration of the knee joint before revision arthroplasty

Not best available

evidence

Dupont, et al.

2008 The value of C-reactive protein for postoperative monitoring of lower limb arthroplasty

Not relevant - not

specific to pji

Eisler, et al.

2001 Ultrasound for diagnosis of infection in revision total hip arthroplasty Insufficient Data


48



Feldman, et al.

1995 The role of intraoperative frozen sections in revision total joint arthroplasty

Not best available

evidence

Forster, et al.

1982 Sedimentation rate in infected and uninfected total hip arthroplasty

Not best available

evidence

Ghanem, et al.

2008 Determining 'true' leukocytosis in bloody joint aspiration

Not best available

evidence

Ghanem, et al.

2009

The use of receiver operating characteristics analysis in determining erythrocyte

sedimentation rate and C-reactive protein levels in diagnosing periprosthetic infection prior

to revision total hip arthroplasty

Not best available

evidence

Ginai, et al.

1996 Digital subtraction arthrography in preoperative evaluation of painful total hip arthroplasty

Not relevant - not

specific to pji

Itasaka, et al.

2001 Diagnosis of infection after total hip arthroplasty

Not best available

evidence

Lachiewicz, et al.

1996

Aspiration of the hip joint before revision total hip arthroplasty. Clinical and laboratory

factors influencing attainment of a positive culture

Not best available

evidence

Levitsky, et al.

1991

Evaluation of the painful prosthetic joint. Relative value of bone scan, sedimentation rate,

and joint aspiration

Not best available

evidence

Lyons, et al.

1985 Evaluation of radiographic findings in painful hip arthroplasties

Not best available

evidence

Magnuson, et al.

1988

In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis infection:

comparison with other imaging modalities

Not best available

evidence

Maury, et al.

1984

Control of the acute-phase serum amyloid A and C-reactive protein response: comparison

of total replacement of the hip and knee

Not relevant - not

diagnostic study

Miniaci, et al.

1990

Analysis of radionuclide arthrograms, radiographic arthrograms, and sequential plain

radiographs in the assessment of painful hip arthroplasty

Not relevant - not

specific to pji


49



Moreschini, et al.

2001

Postoperative physiopathological analysis of inflammatory parameters in patients

undergoing hip or knee arthroplasty

Not relevant - not

diagnostic study

Mulier, et al.

1973 Postoperative infection in total hip replacement

Not best available

evidence

Muller, et al.

2008

Diagnosis of periprosthetic infection following total hip arthroplasty - evaluation of the

diagnostic values of pre- and intraoperative parameters and the associated strategy to

preoperatively select patients with a high probability of joint infection

Not best available

evidence

Nilsdotter-

Augustinsson, et al.

2007

Inflammatory response in 85 patients with loosened hip prostheses: a prospective study

comparing inflammatory markers in patients with aseptic and septic prosthetic loosening

Not best available

evidence

Niskanen, et al.

1996 Serum C-reactive protein levels after total hip and knee arthroplasty

Not relevant - not

diagnostic study

Okafor, et al.

1998

Postoperative changes of erythrocyte sedimentation rate, plasma viscosity and C-reactive

protein levels after hip surgery

Not relevant - not

diagnostic study

Panousis, et al.

2005

Poor predictive value of broad-range PCR for the detection of arthroplasty infection in 92

cases

Not best available

evidence

Park, et al.

2008 Normative Temporal Values of CRP and ESR in Unilateral and Staged Bilateral TKA

Not relevant - not

diagnostic study

Parvizi, et al.

2008 Diagnosis of infected total knee: findings of a multicenter database Insufficient Data

Rosas, et al.

1998

Contribution of laboratory tests, scintigraphy, and histology to the diagnosis of lower limb

joint replacement infection Insufficient Data

Sanzen, et al.

1988 The erythrocyte sedimentation rate following exchange of infected total hips <25 patients/arm

Sanzen, et al.

1989 The diagnostic value of C-reactive protein in infected total hip arthroplasties

Not best available

evidence


50



Sanzen, et al.

1997

Periprosthetic low-grade hip infections. Erythrocyte sedimentation rate and C-reactive

protein in 23 cases <25 patients

Schneider, et al.

1982 Radiologic evaluation of painful joint prostheses

Narrative review,


Schulak, et al.

1982 The erythrocyte sedimentation rate in orthopaedic patients

Narrative review,


Schwenger, et al.

1998 CRP levels in autoimmune disease can be specified by measurement of procalcitonin

Not relevant - not

specific to pji

Sciuk, et al.

1992

White blood cell scintigraphy with monoclonal antibodies in the study of the infected

endoprosthesis

Not best available

evidence

Shih, et al.

1987

Erythrocyte sedimentation rate and C-reactive protein values in patients with total hip

arthroplasty

Not best available

evidence

Simon, et al.

2004

Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a

systematic review and meta-analysis

Not relevant - not

specific to pji

Stumpe, et al.

2004

FDG PET for differentiation of infection and aseptic loosening in total hip replacements:

comparison with conventional radiography and three-phase bone scintigraphy

Not best available

evidence

Sudanese, et al.

1994 Diagnostic protocol in prosthetic loosening

Not best available

evidence

Tehranzadeh, et al.

1981 Radiological evaluation of painful total hip replacement

Not best available

evidence

Teller, et al.

2000 Sequential indium-labeled leukocyte and bone scans to diagnose prosthetic joint infection

Not best available

evidence

Thoren, et al.

1991 Erythrocyte sedimentation rate in infection of total hip replacements

Not best available

evidence

Uzzan, et al.

2006

Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or

trauma: a systematic review and meta-analysis Not relevant


51



Virolainen, et al.

2002 The reliability of diagnosis of infection during revision arthroplasties

Not best available

evidence

Walker, et al.

1991 Arthrography of painful hips following arthroplasty: digital versus plain film subtraction

Not relevant - not

specific to pji

White, et al.

1998 C-reactive protein level after total hip and total knee replacement

Not relevant - not

diagnostic study

STUDY QUALITY

Table 23. Radiography and Serology - Quality

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Savarino 26 ESR (>15mm/hr) I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Savarino 26 ESR (>15mm/hr) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Savarino 26 ESR (>15mm/hr) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Schinsky 201 ESR (>30 mm/hr) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●


52

Table 23. Radiography and Serology – Quality (Continued)

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Savarino 26 ESR (>50 mm/hr) I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Savarino 26 ESR (>50 mm/hr) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Savarino 26 ESR (>50 mm/hr) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Kamme 63 ESR (>30mm/hr) I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Greidanus 151 ESR (>22.5 mm/hr) I ● ● ● ● ● ● ● ● ? ● ● ● ● ●

Greidanus 151 ESR (>30 mm/hr) I ● ● ● ● ● ● ● ● ? ● ● ● ● ●

Bottner 78 ESR (>32 mm/hr) I ● ? ● ● ● ● ● ● ● ● ? ● ● ●

Della Valle 94 ESR (>30 mm/hr) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Savarino 26 CRP (>0.5mg/dL) I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Savarino 26 CRP (>0.5mg/dL) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Savarino 26 CRP (>0.5mg/dL) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Schinsky 201 CRP (>1 mg/dL) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Savarino 26 CRP (>2 mg/dL) I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Savarino 26 CRP (>2 mg/dL) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Savarino 26 CRP (>2 mg/dL) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Greidanus 151 CRP (>1.0 mg/dL) I ● ● ● ● ● ● ● ● ? ● ● ● ● ●


53


● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Greidanus 151 CRP (>1.35 mg/dL) I ● ● ● ● ● ● ● ● ? ● ● ● ● ●

Fink 145 CRP (>1.35 mg/dL) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Bottner 78 CRP (>1.5 mg/dL) I ● ? ● ● ● ● ● ● ● ● ? ● ● ●

Bottner 78 CRP (>3.2 mg/dL) I ● ? ● ● ● ● ● ● ● ● ? ● ● ●

Della Valle 94 CRP (>1 mg/dL) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Greidanus 151 ESR and CRP (22.5/1.35) I ● ● ● ● ● ● ● ● ? ● ● ● ● ●

Greidanus 151 ESR and CRP (30/1.0) I ● ● ● ● ● ● ● ● ? ● ● ● ● ●

Greidanus 151 ESR or CRP (22.5/1.35) I ● ● ● ● ● ● ● ● ? ● ● ● ● ●

Greidanus 151 ESR or CRP (30/1.0) I ● ● ● ● ● ● ● ● ? ● ● ● ● ●

Schinsky 201 ESR or CRP (30/1.0) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Cyteval 65 radiograph - asymmetric

position of femoral head I ● ● ● ● ● ● ● ● ● ● ● ? ● ●

Cyteval 65

radiograph - bone

abnormalities (focal or

nonfocal lucency,

periostitis)

I ● ● ● ● ● ● ● ● ● ● ● ? ● ●

Cyteval 65 radiograph - focal lucency I ● ● ● ● ● ● ● ● ● ● ● ? ● ●


54


● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Cyteval 65 radiograph - nonfocal

lucency I ● ● ● ● ● ● ● ● ● ● ● ? ● ●

Cyteval 65 radiograph - periostitis I ● ● ● ● ● ● ● ● ● ● ● ? ● ●

Bernay 31 radiograph II ● ● ? ● ● ● ● ○ ● ● ? ● ● ●

Barrack 69

radiograph: complete

radiolucent line adjacent to

tibial component

III ● ● ● ● ● ● ● ● ● ● ○ ● ● ●

Barrack 69 radiograph: gross loosening III ● ● ● ● ● ● ● ● ● ● ○ ● ● ●

Barrack 69

radiograph: Knee Society

Grade 3 classification for

tibial component

radiolucency in addition to

Grade 1 under femoral

component

III ● ● ● ● ● ● ● ● ● ● ○ ● ● ●

Barrack 69 radiograph: periostitis III ● ● ● ● ● ● ● ● ● ● ○ ● ● ●

Spangehl 202 WBC (>11.0*10^9/L) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Savarino 26 WBC (>9500/mm^3) I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Savarino 26 WBC (>9500/mm^3) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●


55


● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Savarino 26 WBC (>9500/mm^3) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Pill 92 WBC (>11000/μL) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Spangehl 202 WBC differential (>75%

neutrophils) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Bottner 78 WBC (>6200/μL) I ● ? ● ● ● ● ● ● ● ● ? ● ● ●

Di Cesare 58 WBC (>11.0*10^9) II ● ● ● ● ● ● ● ● ○ ● ? ● ● ●

Bernard 228 Polynuclear neutrophil

count (≥6000 cells/ml) II ? ● ● ● ● ● ● ● ○ ● ● ● ● ○

Trampuz 296 WBC (>10x10^9/L) II ? ● ● ● ● ● ● ● ● ● ? ● ● ○


56

STUDY RESULTS

Figure 5. ESR Meta-analysis Results - Likelihood Ratios

StudyId

COMBINED

Bottner - 32mm/hr

Della Valle - 30mm/hr

Kamme - 30mm/hr

Schinsky - 30mm/hr

Greidanus - 22.5mm/hr

Savarino - 15mm/hr

1 2 5 10

DLR POSITIVE

StudyId

COMBINED

Bottner - 32mm/hr

Della Valle - 30mm/hr

Kamme - 30mm/hr

Schinsky - 30mm/hr

Greidanus - 22.5mm/hr

Savarino - 15mm/hr

1.1 .2 .5

DLR NEGATIVE

INTERPRETING THE FOREST PLOTS

Throughout the guideline we use descriptive diagrams or forest plots to present data from

studies comparing a diagnostic test to a reference standard. The positive and negative

likelihood ratios are the effect measures used to depict study results. The horizontal line

running through each point represents the 95% confidence interval for that point. In the

graphs above, the solid vertical line represents “no effect” where the likelihood ratio is

equal to one. The dashed line represents the value of a likelihood ratio that indicates a

large and conclusive change in the probability of disease.

For example, in the figures above, the summary estimate (indicated by the diamond)

indicates a positive likelihood ratio close to 3 and a negative likelihood ratio of between

0.2 and 0.1. This result is statistically significant because the 95% Confidence Interval

does not cross the “no effect” line. Also please note that summary measures (diamond)

are not reported in the plot if high heterogeneity (>50%) is present.


57

Figure 6. CRP Results - Likelihood Ratios

StudyId

Bottner - 3.2 mg/dL

Savarino - 2 mg/dL

Bottner - 1.5 mg/dL

Greidanus - 1.35 mg/dL

Fink - 1.35 mg/dL

Greidanus - 1 mg/dL

Schinsky - 1 mg/dL

Della Valle - 1 mg/dL

Savarino - 0.5mg/dL

1 2 5 10

DLR POSITIVE

StudyId

Bottner - 3.2 mg/dL

Savarino - 2 mg/dL

Bottner - 1.5 mg/dL

Greidanus - 1.35 mg/dL

Fink - 1.35 mg/dL

Greidanus - 1 mg/dL

Schinsky - 1 mg/dL

Della Valle - 1 mg/dL

Savarino - 0.5mg/dL

1.1.2 .5

DLR NEGATIVE

Figure 7. ESR and CRP - Likelihood Ratios

StudyId

Schinsky – 1 or both positive (30/1.0)

Greidanus – 1 or both positive (30/1.0)

Greidanus – 1 or both positive (22.5/1.35)

Schinsky - both positive (30/1.0)

Greidanus – both positive (30/1.0)

Greidanus – both positive (22.5/1.35)

1 2 5 10

DLR POSITIVE

StudyId

Schinsky – 1 or both positive (30/1.0)

Greidanus – 1 or both positive (30/1.0)

Greidanus – 1 or both positive (22.5/1.35)

Schinsky - both positive (30/1.0)

Greidanus – both positive (30/1.0)

Greidanus – both positive (22.5/1.35)

.1.2 .5 1

DLR NEGATIVE


58

Figure 8. Radiography Results - Likelihood Ratios

StudyId

Cyteval - femoral head asymmetry

Cyteval - bone abnormalities

Cyteval - focal lucency

Cyteval - nonfocal lucency

Cyteval - periostitis

Bernay - plain radiograph

Barrack - radiolucent line

Barrack - gross loosening

Barrack - radiolucency grade

Barrack - periostitis

1 2 5 10

DLR POSITIVE

StudyId



Cyteval - focal lucency

Cyteval - nonfocal lucency


Bernay - plain radiograph

Barrack - radiolucent line

Barrack - gross loosening

Barrack - radiolucency grade

Barrack - periostitis

.1 .2 .5 1

DLR NEGATIVE

Figure 9. White Blood Cell Count Results - Likelihood Ratios

StudyId

Spangehl - WBC count

Savarino

Pill

Spangehl - % neutrophils

Bottner

Di Cesare

Trampuz

Bernard

1 2 5 10

DLR POSITIVE

StudyId

Spangehl - WBC count

Savarino

Pill

Spangehl - % neutrophils

Bottner

Di Cesare

Trampuz

Bernard

1.1 .2 0.5

DLR NEGATIVE


59

Table 24. Erythrocyte Sedimentation Rate Results

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity

(95% CI) TP FN FP TN

I Savarino 26 ESR

(15mm/hr)

Intraoperative

Cultures Hip

0.94

(0.48, 1.82)

1.09

(0.43, 2.8)

0.56

(0.3, 0.8)

0.4

(0.12,

0.74)

9 7 6 4

I Savarino 26 ESR

(15mm/hr) Histology Hip

1.02

(0.53, 1.97)

0.97

(0.39, 2.4)

0.58

(0.28,

0.85)

0.43

(0.18,

0.71)

7 5 8 6

I Savarino 26 ESR

(15mm/hr)

Intraoperative

cultures and

histology

Hip 1.07

(0.55, 2.08)

0.91

(0.36, 2.34)

0.6

(0.26,

0.88)

0.44

(0.2, 0.7) 6 4 9 7

I Schinsky 201

ESR

(30

mm/hr)

at least 2 of: 1)a

positive

intraoperative

culture (on solid

media) 2)gross

purulence 3)final

histopathological

result consistent

with infection

(average of >10

PMN in the 5

most cellular high

power fields)

Hip 1.58

(1.37, 1.82)

0.09

(0.02, 0.37)

0.96

(0.87, 1)

0.39

(0.31,

0.47)

53 2 89 57

I Savarino 26

ESR

(50

mm/hr)

Intraoperative

Cultures Hip

3.75

(0.53,

26.73)

0.69

(0.45, 1.07)

0.38

(0.15,

0.65)

0.9

(0.55, 1) 6 10 1 9


60

Table 24. Erythrocyte Sedimentation Rate Results (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Savarino 26

ESR

(50

mm/hr)

Histology Hip 7

(0.97,

50.27)

0.54

(0.3, 0.97)

0.5

(0.21,

0.79)

0.93

(0.66, 1) 6 6 1 13

I Savarino 26

ESR

(50

mm/hr)

Intraoperative

cultures and

histology

Hip 9.6

(1.35,

68.43)

0.43

(0.2, 0.92)

0.6

(0.26,

0.88)

0.94

(0.7, 1) 6 4 1 15

I Kamme 63 ESR

(30mm/hr)

Intraoperative

Cultures Hip

3.2

(1.69, 6.05)

0.15

(0.06, 0.38)

0.89

(0.75,

0.97)

0.72

(0.51,

0.88)

34 4 7* 18

I Greidanus 151

ESR

(22.5

mm/hr)

Cultures –

Intraoperative

or Aspiration

Knee 5.5

(3.58, 8.43)

0.08

(0.03, 0.24)

0.93

(0.82,

0.99)

0.83

(0.74, 0.9) 42 3 18 88

I Greidanus 151

ESR

(30

mm/hr)

Cultures –

Intraoperative

or Aspiration

Knee

6.7

(3.96,

11.36)

0.2

(0.11, 0.38)

0.82

(0.68,

0.92)

0.88

(0.8, 0.93) 37 8 13 93


61

Table 24. Erythrocyte Sedimentation Rate Results (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Della

Valle 94

ESR

(30

mm/hr)

at least 2 of 3

positive

intraoperative

cultures on

solid media or if

2 of following:

1)at least 1

positive culture

2)final

histopathology

consistent with

infection

3)gross

purulence seen

at time of

revision

Knee 2.66

(1.8, 3.92)

0.15

(0.06, 0.38)

0.9

(0.77,

0.97)

0.66

(0.52,

0.78)

37 4 18 35

I Bottner 78

ESR

(32

mm/hr)

Intraoperative

cultures and

histology

Mixed

(50

hip,

28

knee)

7.69

(3.51,

16.86)

0.21

(0.09, 0.52)

0.81

(0.58,

0.95)

0.89

(0.78,

0.96)

17 4 6 51

*Five false positives were from patients with rheumatoid arthritis, one malignancy, and one with elevated ESR prior to primary operation


62

Table 25. C-Reactive Protein Results

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Savarino 26 CRP

(0.5mg/dL)

Intraoperative

Cultures Hip

1.25

(0.4, 3.9)

0.89

(0.51,

1.56)

0.38

(0.15,

0.65)

0.7

(0.35,

0.93)

6 10 3 7

I Savarino 26 CRP

(0.5mg/dL) Histology Hip

0.93

(0.32,

2.71)

1.04

(0.59,

1.81)

0.33

(0.1, 0.65)

0.64

(0.35,

0.87)

4 8 5 9

I Savarino 26 CRP

(0.5mg/dL)

Intraoperative

cultures and

histology

Hip 0.8

(0.26, 2.5)

1.12

(0.64,

1.95)

0.3

(0.07,

0.65)

0.63

(0.35,

0.85)

3 7 6 10

I Schinsky 201 CRP

(1 mg/dL)

at least 2 of: 1)a

positive

intraoperative

culture (on solid

media) 2)gross

purulence 3)final

histopathological

result consistent

with infection

(average of >10

PMN in the 5

most cellular high

power fields)

Hip 3.29

(2.53,

4.28)

0.08

(0.03,

0.23)

0.95

(0.85,

0.99)

0.71

(0.63,

0.78)

52 3 42 104

I Savarino 26 CRP

(2 mg/dL)

Intraoperative

Cultures Hip

0.94

(0.19,

4.67)

1.02

(0.69, 1.5)

0.19

(0.04,

0.46)

0.8

(0.44,

0.97)

3 13 2 8


63

Table 25. C-Reactive Protein Results (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Savarino 26

CRP

(2

mg/dL)

Histology Hip 4.67

(0.6, 36.29)

0.72

(0.47, 1.1)

0.33

(0.1, 0.65)

0.93

(0.66, 1) 4 8 1 13

I Savarino 26

CRP

(2

mg/dL)

Intraoperative

cultures and

histology

Hip 2.4

(0.48,

11.95)

0.8

(0.51, 1.25)

0.3

(0.07,

0.65)

0.88

(0.62,

0.98)

3 7 2 14

I Greidanus 151

CRP

(1.0

mg/dL)

Cultures –

Intraoperative or

Aspiration

Knee 5.5

(3.58, 8.43)

0.08

(0.03, 0.24)

0.93

(0.82,

0.99)

0.83

(0.74, 0.9) 42 3 18 88

I Greidanus 151

CRP

(1.35

mg/dL)

Cultures –

Intraoperative or

Aspiration

Knee 6.9

(4.2, 11.33)

0.1

(0.04, 0.26)

0.91

(0.79,

0.98)

0.87

(0.79,

0.93)

41 4 14 92

I Fink 145

CRP

(1.35

mg/dL)

Intraoperative

cultures and

histology

Knee 3.81

(2.46, 5.9)

0.34

(0.2, 0.57)

0.73

(0.56,

0.85)

0.81

(0.72,

0.88)

29 11 20 85


64

Table 25. C-Reactive Protein Results (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Della

Valle 94

CRP

(1

mg/dL)

at least 2 of 3

positive

intraoperative

cultures on solid

media or if 2 of

following: 1)at

least 1 positive

culture 2)final

histopathology

consistent with

infection 3)gross

purulence seen at

time of revision

Knee 3.88

(2.41, 6.25)

0.06

(0.02, 0.25)

0.95

(0.83,

0.99)

0.75

(0.62,

0.86)

39 2 13 40

I Bottner 78

CRP

(1.5

mg/dL)

Intraoperative

cultures and

histology

Mixed

(50

hip, 28

knee)

10.86

(4.67,

25.22)

0.05

(0.01, 0.35)

0.95

(0.76, 1)

0.91

(0.81,

0.97)

20 1 5 52

I Bottner 78

CRP

(3.2

mg/dL)

Intraoperative

cultures and

histology

Mixed

(50

hip, 28

knee)

27.14

(6.93, 106)

0.05

(0.01, 0.33)

0.95

(0.76, 1)

0.96

(0.88, 1) 20 1 2 55


65

Table 26. ESR and CRP Results

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Greidanus 151

ESR and

CRP –

positive if

both

positive

(22.5/1.35)

Cultures –

Intraoperative

or Aspiration

Knee 13.5

(6.53, 27.7)

0.12

(0.05, 0.27)

0.89

(0.76,

0.96)

0.93

(0.87,

0.97)

40 5 7 99

I Greidanus 151

ESR and

CRP –

positive if

both

positive

(30/1.0)

Cultures –

Intraoperative

or Aspiration

Knee 12.1

(5.83, 25.2)

0.21

(0.12, 0.38)

0.8

(0.65,

0.90)

0.93

(0.87,

0.97)

36 9 7 99

I Schinsky 201

ESR and

CRP –

positive if

both

positive

(30/1.0)

At least 2 of:

1)positive

intraoperative

culture (on solid

media) 2)gross

purulence

3)final

histopathology

Hip 4.34

(3.11, 6.04)

0.14

(0.06, 0.26)

0.89

(0.78,

0.96)

0.79

(0.72,

0.86)

49 6 30 116

I Greidanus 151

ESR and

CRP –

positive if

one

positive

(22.5/1.35)

Cultures –

Intraoperative

or Aspiration

Knee 4.22

(2.95, 6.03)

0.06

(0.01, 0.22)

0.96

(0.85,

0.99)

0.77

(0.68,

0.85)

43 2 24 82


66

Table 26. ESR and CRP Results (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Greidanus 151

ESR and

CRP –

positive

if one

positive

(30/1.0)

Cultures –

Intraoperative or

Aspiration

Knee 4.22

(2.95, 6.03)

0.06

(0.01, 0.22)

0.96

(0.84,

0.99)

0.77

(0.68,

0.85)

43 2 24 82

I Schinsky 201

ESR and

CRP –

positive

if one

positive

(30/1.0)

At least 2 of:

1)positive

intraoperative

culture (on solid

media) 2)gross

purulence 3)final

histopathology

Hip 1.74

(1.51, 2.0) 0

1

(0.94, 1)

0.43

(0.34,

0.51)

55 0 84 62


67

Table 27. Radiography Results

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Cyteval 65

Radiograph -

asymmetric

position of

femoral head

Intraoperative

Cultures (≥2) Hip

0.52

(0.14, 1.95)

1.23

(0.9, 1.68)

0.17

(0.02,

0.48)

0.68

(0.54, 0.8) 2 10 17 36

I Cyteval 65

Radiograph -

bone

abnormalities

(focal or

nonfocal

lucency,

periostitis)

Intraoperative

Cultures (≥2) Hip

1.05

(0.72, 1.51)

0.88

(0.3, 2.57)

0.75

(0.43,

0.95)

0.28

(0.17,

0.42)

9 3 38 15

I Cyteval 65 Radiograph -

focal lucency

Intraoperative

Cultures (≥2) Hip

1.2

(0.4, 3.66)

0.95

(0.66, 1.35)

0.25

(0.05,

0.57)

0.79

(0.66,

0.89)

3 9 11 42

I Cyteval 65

Radiograph -

nonfocal

lucency

Intraoperative

Cultures (≥2) Hip

0.98

(0.53, 1.83)

1.02

(0.54, 1.91)

0.5

(0.21,

0.79)

0.49

(0.35,

0.63)

6 6 27 26

I Cyteval 65 Radiograph -

periostitis

Intraoperative

Cultures (≥2) Hip

20.77

(1.06, 407)

0.82

(0.62, 1.06)

0.17

(0.02,

0.48)

1

(0.93, 1) 2 10 0 53

II Bernay 31 Radiograph

Pathological

and Gross

Operative

Findings

Hip 2.4

(1.22, 4.74)

0.3

(0.08, 1.07)

0.8

(0.44,

0.97)

0.67

(0.43,

0.85)

8 2 7 14


68

Table 27. Radiography Results (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


III Barrack 69

Radiograph:

complete

radiolucent

line adjacent to

tibial

component

Intraoperative

cultures on

solid media,

aspiration

culture

confirmed by

intraoperative

culture in liquid

media, or

intraoperative

histology

Knee 1.96

(0.59, 6.56)

0.89

(0.7, 1.13)

0.2

(0.06,

0.44)

0.9

(0.78,

0.97)

4 16 5 44

III Barrack 69

Radiograph:

gross

loosening

Intraoperative

cultures on

solid media,

aspiration

culture

confirmed by

intraoperative

culture in liquid

media, or

intraoperative

histology

Knee 0.92

(0.27, 3.11)

1.02

(0.81, 1.27)

0.15

(0.03,

0.38)

0.84

(0.7, 0.93) 3 17 8 41


69

Table 27. Radiography Results (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


III Barrack 69

Radiograph:

Knee Society

Grade 3

classification

for

radiolucency

for the tibial

component in

addition to

Grade 1 under

femoral

component

Intraoperative

cultures on

solid media,

aspiration

culture

confirmed by

intraoperative

culture in liquid

media, or

intraoperative

histology

Knee 2.99

(1.47, 6.1)

0.55

(0.33, 0.91)

0.55

(0.32,

0.77)

0.82

(0.68,

0.91)

11 9 9 40

III Barrack 69 Radiograph:

periostitis

Intraoperative

cultures on

solid media,

aspiration

culture

confirmed by

intraoperative

culture in liquid

media, or

intraoperative

histology

Knee 1.04

(0.73, 1.47)

0.92

(0.42, 2.01)

0.7

(0.46,

0.88)

0.33

(0.2, 0.48) 14 6 33 16


70

Table 28. White Blood Cell Count Results

Level of

Evidence Author N Test Reference Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Spangehl 202 WBC

(11.0x10^9/L

at least 1 of: 1)open

wound of sinus in

communication with the

joint 2)systemic

infection with pain in the

joint and purulent fluid

within the joint

3)positive result on at

least 3

investigations(ESR>30,

CRP>10, preoperative

aspiration with at least 1

positive culture, frozen

section with

>5PMN/HPF,

intraoperative culture

(>1/3 of cultures

positive)

Hip

5.57

(1.99,

15.56)

0.83

(0.7, 0.98)

0.2

(0.08,

0.37)

0.96

(0.92,

0.99)

7 28 6 161

I Savarino 26 WBC

(9500/mm^3) Intraoperative cultures Hip

1.94

(0.09,

43.5)

0.96

(0.79,

1.16)

0.06

(0, 0.3)

1

(0.69, 1) 1 15 0 10

I Savarino 26 WBC

(9500/mm^3) Histology Hip

3.46

(0.15,

77.86)

0.92

(0.74,

1.14)

0.08

(0, 0.38)

1

(0.77, 1) 1 11 0 14

I Savarino 26 WBC

(9500/mm^3)

Intraoperative cultures

and histology Hip

4.64

(0.21,

103.9)

0.89

(0.69,

1.14)

0.1

(0, 0.45)

1

(0.79, 1) 1 9 0 16


71

Table 28. White Blood Cell Count Results (Continued)

Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Pill 92 WBC

(11000/μL)

at least 1 of 3 criteria:

1)an open wound or

sinus communicating

with the joint 2)

systemic infection with

pain in the hip and

purulent fluid within the

joint 3)positive result on

at least 3 tests (ESR,

CRP, joint aspiration,

intraoperative frozen

section, and

intraoperative culture)

Hip 8.45

(1.77,

40.46)

0.78

(0.62, 1)

0.24

(0.08,

0.47)

0.97

(0.9, 1) 5 16 2 69


72


Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Spangehl 202

WBC

differential

(75%

neutrophils)


wound of sinus in

communication with the

joint 2)systemic

infection with pain in

the joint and purulent

fluid within the joint


least 3



aspiration with at least 1

positive culture, frozen

section with

>5PMN/HPF,


(>1/3 of cultures

positive)

Hip 2.01

(0.96,

4.22)

0.87

(0.72,

1.05)

0.23

(0.1, 0.4)

0.89

(0.83,

0.93)

8 27 19 148

I Bottner 78 WBC

(6200/μL)


and histology

Mixed

(50

hip,

28

knee)

1.77

(1.17,

2.68)

0.48

(0.24,

0.97)

0.71

(0.48,

0.89)

0.6

(0.46,

0.72)

15 6 23 34

II Di

Cesare 58

WBC

(11.0x10^9)


and histology Mixed

4.29

(2.38,

7.73)

0.08

(0.01,

0.51)

0.94

(0.71, 1)

0.78

(0.62,

0.89)

16 1 9 32


73


Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


II Trampuz 296 WBC count

(10x10^9/L)

at least 1 of: 1)visible

purulence of synovial

fluid or area

surrounding the

prosthesis 2)acute

inflammation on

histopathologic exam of

permanent

periprosthetic tissue

sections (as determined

by the clinical

pathologist) 3)a sinus

tract communicating

with the prosthesis

Mixed

(207

knee,

124

hip)

3.11

(1.51, 6.4)

0.87

(0.78,

0.97)

0.18

(0.1, 0.29)

0.94

(0.9, 0.97) 13 59 13 211

II Bernard 228

Polynuclear

neutrophil

count

(6000

cells/ml)


Mixed

(167

hip,

63

knee)

2.84

(1.17,

6.92)

0.57

(0.44,

0.73)

0.54

(0.47,

0.61)

0.81

(0.58,

0.95)

112 95 4 17


74

RECOMMENDATION 3 We recommend joint aspiration of patients being assessed for periprosthetic knee

infections that have abnormal erythrocyte sedimentation rate AND/OR C-reactive protein

results. We recommend that the aspirated fluid be sent for microbiologic culture, synovial

fluid white blood cell count and differential.









Rationale

Our systematic review of the literature suggests that ESR/CRP testing is valuable for

screening (ruling out) of periprosthetic infection with extremely high sensitivity (>90%).

These tests are not, however, specific for diagnosis of periprosthetic infection and may be

elevated with any type of infection or inflammation. Hence, for patients with abnormal

ESR/CRP who are being investigated for periprosthetic infection of the knee, the most

appropriate next test is aspiration of the knee joint.

We recommend that the fluid obtained from the joint be sent for analysis of synovial fluid

white blood cell count, percentage of neutrophils, and also culture for aerobic and

anerobic organisms. Studies suggest either synovial fluid white blood cell count over

1700 cells/μl (range, 1100-3000) or neutrophil percentage greater than 65% (range 64%-

80%) is highly suggestive of chronic periprosthetic infection.21, 33, 103

However, the

threshold for cell count and neutrophil percentage indicative of acute periprosthetic joint

infection (within six weeks of index arthroplasty) is yet to be determined and the values

and ranges reported above may not be applicable when diagnosing acute periprosthetic

infections.

Supporting Evidence

Two studies with reliable data addressed the diagnostic efficacy of aspiration cultures

among patients being assessed for periprosthetic knee infections.21, 31†

Both studies

indicated that this test is a good “rule in” test but only moderately good at ruling out

infection (positive likelihood ratio: 14.2-15.2, negative LR: 0.21-0.29; see Table 32).

† Correction: Reference 103 had been cited here incorrectly in a previous version of this document. The

citation has been placed in the correct location in the following paragraph (Research Analyst, 09-30-10).


75

Three studies with reliable data addressed synovial fluid white blood cell count and

differential among patients being assessed for periprosthetic knee infections.21, 33, 103

The

studies indicated that both of these tests are good “rule in” and “rule out” tests (synovial

fluid white blood cell count: LR+: 7.6-35.6, LR

-: 0.01-0.11; differential: LR

+: 6.5-48,

LR-: 0.03-0.05; see Table 33, Table 34).


76

SUMMARY OF EVIDENCE

Table 29. Knee Aspiration Summary of Evidence

Test Number

of Studies

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity

(95% CI)

Aspiration

Cultures

(range)

2 14.2 – 15.2 0.21 – 0.29 0.73 – 0.80 0.94 – 0.95

Synovial fluid

WBC Count

(range)

3 7.6 – 35.6 0.01 – 0.11 0.91 – 1.0 0.88 – 0.98

Synovial fluid

Neutrophil

Percentage

(range)

3 6.5 – 48.0 0.03 – 0.05 0.95 – 0.98 0.85 – 0.98


77

EXCLUDED ARTICLES



Bach, et al.

2002 Total knee arthroplasty infection: significance of delayed aspiration

Does not address

recommendation

Barrack, et al.

1997 The Coventry Award. The value of preoperative aspiration before total knee revision

Not best available

evidence

Duff, et al.


Not best available

evidence

Kersey, et al.

2000

White blood cell counts and differential in synovial fluid of aseptically failed total knee

arthroplasty

Does not address

recommendation

Mason, et al.

2003 The value of white blood cell counts before revision total knee arthroplasty

Not best available

evidence

Parvizi, et al.

2006 Periprosthetic infection: What are the diagnostic challenges?

Not best available

evidence

Parvizi, et al.

2008 Diagnosis of infected total knee: findings of a multicenter database

Not best available

evidence

Trampuz, et al.

2006

Sonication of explanted prosthetic components in bags for diagnosis of prosthetic joint

infection is associated with risk of contamination

Not best available

evidence

Trampuz, et al.

2007 Sonication of removed hip and knee prostheses for diagnosis of infection

Not best available

evidence

Van den Bekerom,

et al. 2006

The value of pre-operative aspiration in the diagnosis of an infected prosthetic knee: a

retrospective study and review of literature

Not best available

evidence

Virolainen, et al.


Not best available

evidence


78

STUDY QUALITY

Table 31. Knee Aspiration - Quality

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Della Valle 94 Aspiration culture I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Fink 145 Aspiration culture I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Della Valle 94 Synovial fluid WBC

count (>3000/μL) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Ghanem 429 Synovial fluid WBC

count (>1100/μL) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Trampuz 133 Synovial fluid WBC

count (>1700/μL) I ? ● ● ● ● ● ● ● ● ● ? ● ● ●

Della Valle 94

Synovial fluid WBC

differential (>65%

PMN)

I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Ghanem 429 Synovial fluid %

neutrophil (>64%) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Trampuz 133 Synovial fluid %

neutrophil (>65%) I ? ● ● ● ● ● ● ● ● ● ? ● ● ●


79

STUDY RESULTS

Table 32. Aspiration Culture - Knee

Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Della

Valle 94

Aspiration

culture on

solid media

At least 2 of 3 positive

intraoperative cultures

on solid media or 2 of

following: 1)at least 1

positive culture 2)final

histopathology

consistent with

infection 3)gross

purulence at revision

Knee

14.22

(4.69,

43.12)

0.21

(0.11, 0.39)

0.8

(0.65,

0.91)

0.94

(0.84,

0.99)

3 3 8 50

I Fink 145 Aspiration

culture

Intraoperative Cultures

and Histology Knee

15.23

(6.34,

36.58)

0.29

(0.17, 0.48)

0.73

(0.56,

0.85)

0.95

(0.89,

0.98)

29 5 11 100


80

Table 33. Synovial Fluid White Blood Cell Count

Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Della

Valle 94

WBC

(3.0x10^3/μL)

At least 2 of 3

positive

intraoperative

cultures on solid

media or 2 of

following: 1)at least

1 positive culture

2)final

histopathology

consistent with

infection 3)gross


Knee

35.57

(7.34,

172.4)

0.01

(0, 0.19)

1

(0.91, 1)

0.98

(0.9, 1) 41 0 1 52


81

Table 33. Synovial Fluid White Blood Cell Count (Continued)

Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Ghanem 429

WBC

(1.1x10^3

/μL)


1)presence of an

abscess or sinus tract

communicating with the

joint space 2)positive

culture of aspirate on

solid medium 3)≥2

positive intraoperative

cultures of the same

organism, or one

positive culture on solid

medium and the

presence of gross

intracapsular purulence

or abnormal histological

findings; when cultures

were negative, infection

was present if had both

grossly purulent fluid

and an abnormal frozen

section (Mirra et al.

criteria)

Knee

7.59

(5.47,

10.55)

0.11

(0.07, 0.17)

0.91

(0.85,

0.95)

0.88

(0.84,

0.92)

146 32 15 236


82


Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Trampuz 133

WBC

(1.7x10^3

/μL)

at least 1 of the

following criteria:

growth of the same

microorganism in at

least 2 cultures of

synovial fluid or

periprosthetic tissue;

visible synovial fluid

purulence at the time of

arthrocentesis or during

surgery; acute

inflammation on

histopathologic

examination of

permanent


sections; or presence of

a sinus tract

communicating with the

prosthesis

Knee

7.76

(4.54,

13.28)

0.07

(0.02, 0.26)

0.94

(0.8, 0.99)

0.88

(0.8, 0.94) 32 12 2 87

Note: Authors of other articles49, 66

investigating synovial fluid cell counts who expressed counts in milliliters (ml) were contacted; they confirmed

that the units reported for the cell count in the published report were incorrect. The actual units to indicate periprosthetic infection were microliters

(µl) and fall within the limits cited above.90

Although the units to express cell count differs between published reports, the American College of

Rheumatology (ACR) recommends that cell count be expressed as cells/μl.90


83

Table 34. Synovial Fluid Neutrophil Percentage

Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Della

Valle 94

>65%

PMN

At least 2 of 3 positive

intraoperative cultures on

solid media or 2 of

following: 1)at least 1

positive culture 2)final

histopathology consistent

with infection 3)gross


Knee

6.46

(3.41,

12.26)

0.03

(0, 0.2)

0.98

(0.87, 1)

0.85

(0.72, 0.93) 40 8 1 45


84

Table 34. Synovial Fluid Neutrophil Percentage (Continued)

Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Ghanem 429 > 64%

Neutrophils


1)presence of an

abscess or sinus tract

communicating with

the joint space

2)positive culture of

aspirate on solid

medium 3)≥2 positive


of the same organism,

or one positive culture

on solid medium and

the presence of gross

intracapsular

purulence or abnormal

histological findings;

when cultures were

negative, infection

was present if had

both grossly purulent

fluid and an abnormal

frozen section (Mirra

et al. criteria)

Knee

18.19

(10.91,

30.33)

0.05

(0.03, 0.1)

0.95

(0.9, 0.98)

0.95

(0.91,

0.97)

153 14 8 254


85


Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Trampuz 133 > 65%

Neutrophils

at least 1 of the

following criteria:

growth of the same

microorganism in at

least 2 cultures of

synovial fluid or

periprosthetic tissue;

visible synovial fluid

purulence at the time

of arthrocentesis or

during surgery; acute

inflammation on

histopathologic

examination of

permanent


sections; or presence

of a sinus tract

communicating with

the prosthesis

Knee

48.04

(12.17,

189.65)

0.03

(0, 0.21)

0.97

(0.85, 1)

0.98

(0.93, 1) 33 2 1 97


86

RECOMMENDATION 4 We recommend a selective approach to aspiration of the hip based on the patient’s

probability of periprosthetic joint infection and the results of the erythrocyte

sedimentation rate (ESR) AND C-reactive protein (CRP). We recommend that the

aspirated fluid be sent for microbiologic culture, synovial fluid white blood cell count and

differential.

Selection of Patients for Hip Aspiration

Probability of

Infection

ESR and CRP

Results

Planned Reoperation

Status Recommended Test

Higher + + or + − Planned or not planned Aspiration

Lower + + or + − Planned Aspiration or Frozen Section

Lower + + Not planned Aspiration

Lower + − Not planned Please see Recommendation 6

Higher or Lower − − Planned or not planned No further testing

Key for ESR and CRP results

+ + = ESR and CRP test results are abnormal

+ − = either ESR or CRP test result is abnormal

− − = ESR and CRP test results are normal









Rationale

AAOS conducted a systematic review that identified six Level I hip,4, 27, 57, 65, 68, 111

and

one hip and knee study35

on the diagnostic performance of hip aspiration and culture.

(Please see Recommendation 3 for data supporting knee patients.) These studies did not

stratify patients as to whether they were at higher or lower probability for infection, and

all patients underwent re-operation. The indications for patients having an aspiration

varied between studies, with aspiration often a routine part of preoperative investigations.

Our meta-analysis indicated that hip aspiration for culture has a moderate to large ability

to “rule in” infection but a small to moderate ability to “rule out” infection (positive

likelihood ratio 9.8, negative LR 0.33). Based on the meta-analysis, hip aspiration is a

useful test to diagnose periprosthetic hip infection. Therefore, we recommend hip


87

aspiration in all “higher probability or lower probability” patients undergoing reoperation

of the hip with abnormal ESR and/or CRP results. 4, 27, 35, 57, 65, 68, 111

Given the potential problems with instituting treatment and missing the diagnosis of

infection, “higher probability” patients with an abnormal ESR AND/OR CRP without

planned reoperation should also receive hip aspiration.

There is no reliable evidence, however, on the diagnostic performance of hip aspirations

in patients who are not to undergo reoperation. Possible harms include the possibility of

false positive results, the possibility of the introduction of bacteria into the joint during

the procedure and patient pain and/or discomfort while undergoing the procedure.4 There

are also concerns about the cost of the procedure.4 Therefore, universal hip aspiration

does not seem indicated. Aspiration is indicated for lower probability hip patients without

planned reoperation only if both ESR AND CRP levels are abnormal. Lower probability

hip arthroplasty patients without planned reoperation who have an abnormal ESR OR

CRP are addressed in Recommendation 6.

We do not recommend that “higher or lower probability” patients with normal ESR and

CRP have hip aspiration prior to planned reoperation.

Supporting Evidence

Six studies of hip patients4, 27, 57, 65, 68, 111

and one study of mixed hip and knee (80%

hip)35

patients, all with reliable data, addressed the diagnostic efficacy of hip aspiration

cultures. Our meta-analysis of these studies indicated that this test is a good “rule in”

test, but not as good at ruling out infection (LR+: 9.8, LR

-: 0.33; see Figure 10). The

indications for patients having an aspiration varied between studies, with aspiration often

a routine part of preoperative investigations. Two studies reported that patients were off

antibiotics for at least two weeks prior to aspiration.4, 35

Three studies reported injecting

saline for re-aspiration,35, 68, 111

while three studies reported not doing so.4,

27,

57

Two studies of hip patients with reliable data addressed synovial fluid white blood cell

count and differential.96, 99

The data from these studies indicated that synovial fluid white

blood cell count is a good “rule in” and possibly a good “rule out” test (LR+: 12-55, LR

-:

0.18-0.65; see Figure 11). The higher threshold used in one study99

may account for its

higher negative likelihood ratio (0.65). Neutrophil percentage (both studies used an 80%

threshold) was a moderately good “rule in” and “rule out” test (LR+: 4.8-5.9, LR

-: 0.13-

0.22; see Figure 12).

None of the results presented includes data based on the use of diagnostic arthrography.

SUMMARY OF EVIDENCE

Table 35. Aspiration Summary of Evidence

Test Number

of Studies

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity

(95% CI)


88

Test Number

of Studies

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity

(95% CI)

Aspiration

Cultures

(I2=0%)

7 9.8

(5.4, 17.9)

0.33

(0.18, 0.60)

0.69

(0.50, 0.84)

0.93

(0.89, 0.95)

Synovial fluid

WBC Count

(range)

2 12.2 – 55.4 0.18 – 0.65 0.36 – 0.84 0.93 – 0.99

Synovial fluid

Neutrophil

Percentage

(range)

2 4.8 – 5.9 0.13 – 0.22 0.82 – 0.89 0.83 – 0.85

*Range presented when fewer than four studies


89

EXCLUDED ARTICLES



Ali, et al.

2006

Accuracy of joint aspiration for the preoperative diagnosis of infection in total hip

arthroplasty

Not best available

evidence

Bernard, et al.

2004

Value of preoperative investigations in diagnosing prosthetic joint infection: retrospective

cohort study and literature review

Not best available

evidence

Buchholz, et al.

1981 Management of deep infection of total hip replacement

Not best available

evidence

Cheung, et al.

1997

The role of aspiration and contrast-enhanced arthrography in evaluating the uncemented

hip arthroplasty

Not best available

evidence

Chryssikos, et al.

2008 FDG-PET imaging can diagnose periprosthetic infection of the hip

Not best available

evidence

Dussault, et al.

1977 Radiologic diagnosis of loosening and infection in hip prostheses Insufficient Data

Fehring, et al.

1996 Aspiration as a guide to sepsis in revision total hip arthroplasty

Not best available

evidence

Gelman,

1976 Arthrography in total hip prosthesis complications

Case

report/commentary

Gould, et al.

1990 Role of routine percutaneous hip aspirations prior to prosthesis revision

Not best available

evidence

Guercio, et al.

1990

Arthrography of the prosthesetized painful hip: the importance of imaging and functional

testing

Does not address

recommendation

Itasaka, et al.


Not best available

evidence

Johnson, et al.

1988

Detection of occult infection following total joint arthroplasty using sequential technetium-

99m HDP bone scintigraphy and indium-111 WBC imaging

Not best available

evidence


90



Kraemer, et al.

1993

Bone scan, gallium scan, and hip aspiration in the diagnosis of infected total hip

arthroplasty

Not best available

evidence

Levitsky, et al.

1991

Evaluation of the painful prosthetic joint. Relative value of bone scan, sedimentation rate,

and joint aspiration

Not best available

evidence

Lieberman, et al.

1993 Evaluation of painful hip arthroplasties. Are technetium bone scans necessary?

Not best available

evidence

Lyons, et al.

1985 Evaluation of radiographic findings in painful hip arthroplasties

Not best available

evidence

Magnuson, et al.

1988

In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis infection:

comparison with other imaging modalities

Not best available

evidence

Maus, et al.

1987 Arthrographic study of painful total hip arthroplasty: refined criteria Insufficient Data

McLaughlin, et al.

1977 Evaluation of the painful hip by aspiration and arthrography Insufficient Data

Muller, et al.

2008




Not best available

evidence

Murray, et al.

1975

Arthrography for the assessment of pain after total hip replacement. A comparison of

arthrographic findings in patients with and without pain <25 patients

O'Neill, et al.

1984

Failed total hip replacement: assessment by plain radiographs, arthrograms, and aspiration

of the hip joint

Not best available

evidence

Phillips, et al.

1983 Efficacy of preoperative hip aspiration performed in the radiology department

Not best available

evidence

Pons, et al.

1999 Infected total hip arthroplasty--the value of intraoperative histology

Not best available

evidence


91



Roberts, et al.

1992

Diagnosing infection in hip replacements. The use of fine-needle aspiration and

radiometric culture

Not best available

evidence

Salenius, et al.

1979

Arthrography of the hip in the diagnosis of postoperative painful conditions after total hip

replacement

Does not address

recommendation

Salvati, et al.

1971

Arthrography for complications of total hip replacement. A review of thirty-one

arthrograms Insufficient Data

Somme, et al.

2003

Contribution of routine joint aspiration to the diagnosis of infection before hip revision

surgery

Not best available

evidence

Taylor, et al.

1995 Fine needle aspiration in infected hip replacements

Not best available

evidence

Teller, et al.

2000 Sequential indium-labeled leukocyte and bone scans to diagnose prosthetic joint infection

Not best available

evidence

Tigges, et al.

1993

Hip aspiration: a cost-effective and accurate method of evaluating the potentially infected

hip prosthesis

Not best available

evidence


92

STUDY QUALITY

Table 37. Aspiration - Quality

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Barrack 291 Aspiration culture I ● ● ● ● ● ● ● ● ? ● ? ● ● ●

Barrack 260 aspiration (initial) I ● ● ● ● ● ● ● ● ? ● ? ● ● ●

Barrack 31 aspiration (repeat) I ● ● ● ● ● ● ● ● ? ● ? ● ● ●

Eisler 57 Aspiration culture I ? ● ● ● ● ● ● ● ● ● ● ● ● ●

Glithero 54 Aspiration culture I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Lachiewicz 156 Aspiration culture I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Malhotra 41 Aspiration culture I ? ● ● ● ● ● ● ● ● ● ? ● ● ●

Mulcahy 71 Aspiration culture I ? ● ● ● ● ● ● ● ● ● ? ● ● ●

Williams 273 Aspiration culture I ? ● ● ● ● ● ● ● ● ● ● ● ● ●


93

Table 37. Aspiration – Quality (Continued)

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Schinsky 201 Synovial fluid WBC

count (>4200/μl) I ● ● ● ● ● ● ● ? ● ● ? ● ● ●

Spangehl 183 Synovial fluid WBC

count (>50000/μL) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Schinsky 201

Synovial fluid WBC

differential (>80%

PMN)

I ● ● ● ● ● ● ● ? ● ● ? ● ● ●

Spangehl 181 Synovial fluid %

neutrophils (>80%) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●


94

STUDY RESULTS

Figure 10. Hip Aspiration Cultures Results - Meta-Analysis

StudyId

COMBINED

Lachiewicz

Williams

Mulcahy

Eisler

Malhotra

Barrack

Glithero

1 2 5 10

DLR POSITIVE

StudyId

COMBINED

Lachiewicz

Williams

Mulcahy

Eisler

Malhotra

Barrack

Glithero

1.1 .2 .5

DLR NEGATIVE


95

Figure 11. Synovial Fluid WBC Count Results - Likelihood Ratios (Hip and Knee)

StudyId

Spangehl (hip)- 50000/uL

Schinsky (hip) - 4200/uL

Della Valle (knee)- 3000/uL

Trampuz (knee) - 1700/uL

Ghanem (knee)- 1100/uL

1 2 510

DLR POSITIVE

StudyId

Spangehl (hip) - 50000/uL

Schinsky (hip) - 4200/uL

Della Valle (knee) - 3000/uL

Trampuz (knee) - 1700/uL

Ghanem (knee) - 1100/uL

1.1.2 .5

DLR NEGATIVE

Figure 12. Neutrophil Percentage Results – Likelihood Ratios (Hip and Knee)

StudyId

Spangehl (hip)

Schinsky (hip)

Ghanem (knee)

Trampuz (knee)

Della Valle (knee)

1 2 5 10

DLR POSITIVE

StudyId

Spangehl (hip)

Schinsky (hip)

Ghanem (knee)

Trampuz (knee)

Della Valle (knee)

.1 .2 .5 1

DLR NEGATIVE


96

Table 38. Aspiration Culture - Hip

Level of


Positive

Likelihood

Ratio (95%

CI)

Negative

Likelihood

Ratio (95%

CI)

Sensitivity

(95% CI)

Specificity


I Barrack 291 Aspiration

culture

Correlation between


and histology; the

appearance of the

tissue

intraoperatively; and

the clinical course

Hip 5.11

(2.81, 9.3)

0.45

(0.21, 0.97)

0.6

(0.26, 0.88)

0.88

(0.84, 0.92) 6 33 4 248


(initial)

Correlation between


and histology; the

appearance of the

tissue


the clinical course

Hip 4

(1.42, 11.23)

0.57

(0.21, 1.52)

0.5

(0.07, 0.93)

0.88

(0.83, 0.91) 2 33 2 224


(repeat)

Correlation between


and histology; the

appearance of the

tissue


the clinical course

Hip

16.67

(2.25,

123.39)

0.35

(0.11, 1.08)

0.67

(0.22, 0.96)

0.96

(0.8, 1) 4 1 2 24


97

Table 38. Aspiration Culture (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio (95%

CI)

Negative

Likelihood

Ratio (95%

CI)

Sensitivity

(95% CI)

Specificity


I Eisler 57 Aspiration

culture

Intraoperative

Cultures Hip

2.16

(0.12, 39.05)

0.94

(0.7, 1.27)

0

(0, 0.6)

0.96

(0.87, 1) 0 2 4 51

I Glithero 54 Aspiration

culture

Intraoperative

Cultures

Mixed

(43

hip, 11

knee)

31.32

(4.51, 217)

0.11

(0.03, 0.4)

0.89

(0.67, 0.99)

0.97

(0.85, 1) 17 1 2 34

I Lachiewicz 156 Aspiration

culture

Intraoperative

Cultures or

Gross

Purulence

Hip

27.47

(10.34,

73.01)

0.15

(0.06, 0.38)

0.85

(0.66, 0.96)

0.97

(0.92, 0.99) 23 4 4 125

I Malhotra 41 Aspiration

culture Histology Hip

4.74

(1.29, 17.42)

0.61

(0.34, 1.11)

0.44

(0.14, 0.79)

0.91

(0.75, 0.98) 4 3 5 29

I Mulcahy 71 Aspiration

culture

Intraoperative

Cultures and

Histology

Hip 7.56

(3.08, 18.58)

0.34

(0.17, 0.71)

0.69

(0.41, 0.89)

0.91

(0.8, 0.97) 11 5 5 50

I Williams 273 Aspiration

culture

Intraoperative

Cultures Hip

12.47

(7.28, 21.37)

0.21

(0.13, 0.34)

0.8

(0.69, 0.89)

0.94

(0.89, 0.97) 57 13 14 189


98

Table 39. Synovial Fluid White Blood Cell Count

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Schinsky 201 WBC

(4.2x10^3/μl)

At least 2 of: 1)a

positive

intraoperative

culture (on solid

media) 2)gross

purulence 3)final

histopathology

Hip

12.21

(6.64,

22.46)

0.18

(0.1, 0.32)

0.84

(0.71,

0.92)

0.93

(0.88,

0.97)

46 10 9 136

I Schinsky 79

WBC

(3.0x10^3/μl),

among

patients with

elevated ESR

and CRP

At least 2 of: 1)a

positive

intraoperative

culture (on solid

media) 2)gross

purulence 3)final

histopathology

Hip 8.98

(3.06, 26.4)

0.11

(0.05, 0.26)

0.90

(0.78,

0.97)

0.90

(0.73,

0.98)

44 3 5 27

I Schinsky 79

WBC

(9.0x10^3/μl),

among

patients with

elevated ESR

and CRP

At least 2 of: 1)a

positive

intraoperative

culture (on solid

media) 2)gross

purulence 3)final

histopathology

Hip 8.16

(2.77, 24.1)

0.20

(0.11, 0.37)

0.82

(0.68,

0.91)

0.90

(0.73,

0.98)

40 3 9 27


99


Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Schinsky 60

WBC

(3.0x10^3/μl),

among

patients with

elevated ESR

or CRP, not

both

At least 2 of: 1)a

positive

intraoperative

culture (on solid

media) 2)gross

purulence 3)final

histopathology

Hip 6.43

(2.95, 14)

0.19

(0.03,

1.15)

0.83

(0.36, 1)

0.87

(0.75,

0.95)

5 7 1 47

I Schinsky 60

WBC

(9.0x10^3/μl),

among

patients with

elevated ESR

or CRP, not

both

At least 2 of: 1)a

positive

intraoperative

culture (on solid

media) 2)gross

purulence 3)final

histopathology

Hip 86.4

(5.3, 1402)

0.22

(0.05,

0.89)

0.83

(0.36, 1)

1

(0.93, 1) 5 0 1 54


100


Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Spangehl 183 WBC

(5.0x10^4/μL)


wound of sinus in

communication with

the joint 2)systemic

infection with pain

in the joint and

purulent fluid within

the joint 3)positive

result on at least 3

investigations(ESR,

CRP, preoperative

aspiration, frozen

section,

intraoperative

cultures

Hip

55.36

(7.37,

415.6)

0.65

(0.49,

0.85)

0.36

(0.19,

0.56)

0.99

(0.96, 1) 10 1 18 154


101

Table 40. Synovial Fluid Neutrophil Percentage

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Schinsky 201 >80%

PMN

At least 2 of:

1)positive

intraoperative

culture (on solid

media) 2)gross

purulence 3)final

histopathology

Hip 4.78

(3.27, 6.97)

0.22

(0.12, 0.39)

0.82

(0.69, 0.91)

0.83

(0.76, 0.89) 45 25 10 121

I Schinsky 79

>80%

PMN,

among

patients

with

elevated

ESR and

CRP

At least 2 of:

1)positive

intraoperative

culture (on solid

media) 2)gross

purulence 3)final

histopathology

Hip 8.78

(2.98, 25.8)

0.14

(0.06, 0.29)

0.88

(0.75, 0.95)

0.90

(0.73, 0.98) 43 3 6 27


102


Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Spangehl 181 >80%

Neutrophils


wound of sinus in

communication with






least 3 investigations

(ESR, CRP,

preoperative

aspiration, frozen

section, intraoperative

cultures

Hip 5.94

(3.99, 8.84)

0.13

(0.04, 0.37)

0.89

(0.72,

0.98)

0.85

(0.78, 0.9) 25 23 3 130


103

RECOMMENDATION 5 We suggest a repeat hip aspiration when there is a discrepancy between the probability of

periprosthetic joint infection and the initial aspiration culture result.


Description: Evidence from two or more “Moderate” strength studies with consistent findings, or

evidence from a single “High” quality study for recommending for or against the intervention. A

Moderate recommendation means that the benefits exceed the potential harm (or that the

potential harm clearly exceeds the benefits in the case of a negative recommendation), but the

strength of the supporting evidence is not as strong.

Implications: Practitioners should generally follow a Moderate recommendation but remain alert

to new information and be sensitive to patient preferences.

Rationale

A repeat hip aspiration is suggested when there is a discrepancy between the clinical

probability of infection and the result of the initial aspiration culture.

One Level I study addressed this recommendation. This study examined performing a

repeat hip aspiration in 28 patients because their initial aspiration result conflicted with

the clinical suspicion for periprosthetic infection.4 This report suggests that repeat

aspiration of the hip be considered when 1) the clinical probability of infection is low but

the initial aspiration culture result is positive, or 2) if the clinical probability of infection

is high and the initial aspiration culture result is negative (see Supporting Evidence

below, for details).

The results of additional tests will raise or lower the probability of periprosthetic

infection. The study on which this recommendation is based predated the more routine

use and acceptance of synovial fluid white blood cell count and differential. Thus,

depending on the results of the synovial fluid white blood cell count and differential, as

well as the ESR and CRP, the diagnosis or exclusion of periprosthetic infection may be

apparent and repeat aspiration may not be necessary.

Supporting Evidence

One study4 with reliable data performed repeat aspiration in 28 patients because the

initial aspiration results contradicted clinical suspicions: 25 patients had a positive initial

culture but no clinical or radiographic indication of infection while 3 patients had either a

negative culture or a culture positive for S. epidermidis only but infection was clinically

suspected. 24 of the 25 with a positive initial culture had a negative repeat aspiration; the

other had a false positive repeat aspiration. The three patients with suspected infection

each had two repeat aspirations. The second aspiration was negative in two and positive

in one, while the third aspiration was positive in all three. Repeat aspiration was

attempted but no fluid was obtained in five additional hips. The results are presented in

Table 43.


104

EXCLUDED ARTICLES



Fehring, et al.

1996 Aspiration as a guide to sepsis in revision total hip arthroplasty <25 patients

Glithero, et al.

1993 White cell scans and infected joint replacements. Failure to detect chronic infection <25 patients

Lachiewicz, et al.

1996

Aspiration of the hip joint before revision total hip arthroplasty. Clinical and laboratory

factors influencing attainment of a positive culture <25 patients

Somme, et al.

2003

Contribution of routine joint aspiration to the diagnosis of infection before hip revision

surgery <25 patients

Spangehl, et al.

1999

Prospective analysis of preoperative and intraoperative investigations for the diagnosis of

infection at the sites of two hundred and two revision total hip arthroplasties <25 patients

Taylor, et al.

1995 Fine needle aspiration in infected hip replacements <25 patients


105

STUDY QUALITY

Table 42. Repeat Aspiration - Quality

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Barrack 260 aspiration (initial) I ● ● ● ● ● ● ● ● ? ● ? ● ● ●

Barrack 31 aspiration (repeat) I ● ● ● ● ● ● ● ● ? ● ? ● ● ●

STUDY RESULTS

Table 43. Repeat Aspiration Results

Level of

Evidence Author N Test Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio (95%

CI)

Sensitivity

(95% CI)

Specificity


I Barrack 260 Initial

Aspiration Hip

4

(1.42, 11.23)

0.57

(0.21, 1.52)

0.5

(0.07, 0.93)

0.88

(0.83,

0.91)

2 33 2 224

I Barrack 31 Repeat

Aspiration Hip

16.67

(2.25, 123.4)

0.35

(0.11, 1.08)

0.67

(0.22, 0.96)

0.96

(0.8, 1) 4 1 2 24


106

RECOMMENDATION 6 In the absence of reliable evidence, it is the opinion of the work group that lower

probability hip arthroplasty patients without planned reoperation who have abnormal

erythrocyte sedimentation rates OR abnormal C-reactive protein levels be re-evaluated

for infection within three months. We are unable to recommend specific diagnostic tests

at the time of this follow-up.










Rationale

In the opinion of the work group, the possible harms associated with performing hip

aspiration need to be weighed when conflicting erythrocyte sedimentation rates OR

abnormal C-reactive protein levels are found in the patient. Lower probability hip

arthroplasty patients without planned reoperation who have an abnormal ESR OR CRP

are to be re-evaluated within three months. If the patient is asymptomatic, further testing

may not be necessary.

Hip aspiration is a useful test to diagnose periprosthetic hip infection in patients who

have a higher probability of infection and abnormal ESR or CRP as referenced in

Recommendation 4. However, possible harms of joint aspiration include the possibility of

false positive results, the possibility of the introduction of bacteria into the joint during

the procedure and patient pain and/or discomfort while undergoing the procedure.4 There

are also concerns about the cost of the procedure.4 Lower probability hip arthroplasty

patients without planned reoperation who have an abnormal ESR OR CRP are to be re-

evaluated within three months.

There is insufficient evidence to address whether further observation alone, diagnostic

testing, or both can be recommended based on lack of available evidence to address the

recommendation.

Hip arthroplasty patients at a lower probability of infection who have an isolated

elevation in ESR OR CRP levels but without other objective or subjective evidence of

periprosthetic infection include patients who have a known unrelated cause for this

elevation. Such patients may not require future observation. However, this patient group

also includes the low-grade subclinical infection or early onset periprosthetic infection

that has not fully declared itself.


107

Because of the often insidious nature of periprosthetic infection, the orthopedic surgeon

will need to use clinical judgment in each individual case. Options to consider include

simple future observation with repeat ESR and CRP testing and reentering the patient

into the diagnostic algorithm versus attempting to immediately establish the presence or

absence of periprosthetic infection with additional testing. Discussion of available

diagnostic procedures applicable to the individual patient relies on mutual

communication between the patient and physician, weighing the potential risks and

benefits for that patient. The ultimate judgment regarding any specific procedure or

treatment must be made in light of all circumstances presented by the patient.

Supporting Evidence

We found no data specific to this patient population.


108

RECOMMENDATION 7 In the absence of reliable evidence, it is the opinion of the work group that a repeat knee

aspiration be performed when there is a discrepancy between the probability of

periprosthetic joint infection and the initial aspiration culture result.










Rationale

It was the consensus of the work group that data be extrapolated from recommendation 5

for periprosthetic knee infections even though there was no reliable evidence pertaining

to the utility of a repeat knee aspiration. (The available study5 enrolled too few patients to

be reliable.)

It is the opinion of the work group that repeat aspiration be performed when 1) the

clinical probability of infection is low but the initial aspiration culture result is positive,

or 2) if the clinical probability of infection is high and the initial aspiration culture result

is negative.

The final decision on whether to perform a repeat knee aspiration may also be influenced

by other factors. The results of additional tests will raise or lower the probability of

periprosthetic infection. Thus, depending on the results of ESR and CRP, as well as the

synovial fluid white blood cell count and differential, the diagnosis or exclusion of

periprosthetic infection may be more apparent and repeat aspiration may not be

necessary.

Supporting Evidence

No studies met the inclusion criteria for this recommendation.

EXCLUDED ARTICLES

Table 44. Excluded Article - Recommendation 7

Author Title Reason for

Exclusion

Barrack, et al.

1997

The Coventry Award. The value of preoperative

aspiration before total knee revision <25 patients


109


110

RECOMMENDATION 8 We suggest patients be off of antibiotics for a minimum of 2 weeks prior to obtaining

intra-articular culture.









Rationale

Culture “yield” (isolation of infecting organism) is lower in patients who are receiving or

have recently (within two weeks) received antibiotics.105

This may be because elution of

antibiotics into the joint fluid interferes with isolating the infecting organism by culture.

Although, the exact “antibiotic-free” time needed to allow ”wash-out” of antibiotics from

systemic circulation and the joint is not known, the work group has accepted two weeks

as the minimum time required. One study showed that the false negative rate of cultures

was significantly higher in patients who received antibiotics within two weeks of

aspiration of a joint.105

Supporting Evidence

One included study with reliable data addressed whether antibiotic therapy decreases the

sensitivity of intraoperative cultures in diagnosing periprosthetic infection.105

The group

of patients who had received antimicrobial therapy within 14 days of surgery had a

statistically significantly higher rate of false-negative culture results than those who had

not. In this study, a positive result was defined as growth from at least two specimens.


111

EXCLUDED ARTICLES



Barrack, et al.

1997 The Coventry Award. The value of preoperative aspiration before total knee revision <25 patients/arm

Datz, et al.

1986 Effect of antibiotic therapy on the sensitivity of indium-111-labeled leukocyte scans

Not relevant - not

specific to pji

Spangehl, et al.

1999


infection at the sites of two hundred and two revision total hip arthroplasties <25 patients/arm

Spangehl, et al.

1999

The role of intraoperative gram stain in the diagnosis of infection during revision total hip


Trampuz, et al.

2006


infection is associated with risk of contamination <25 patients


112

STUDY QUALITY

Table 46. Preoperative Antibiotic Therapy - Quality

● = Yes

○ = No

? =Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Trampuz 78 Intraoperative

Cultures (≥2) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

STUDY RESULTS

Table 47. Preoperative Antibiotics and False-Negative Cultures

Level of

Evidence Author N Joint Reference Standard False Negatives Risk Ratio

p-

value

I Trampuz 79 Mixed

At least 1 of: 1)visible purulence of synovial

fluid or area surrounding the prosthesis

2)acute inflammation on histopathologic

exam of permanent periprosthetic tissue

sections 3)a sinus tract communicating with

the prosthesis

Antibiotics within 14 days: 55%

No antibiotics within 14 days: 23%

2.38

(1.26,

4.51)

0.004


113

RECOMMENDATION 9 Nuclear imaging (Labeled leukocyte imaging combined with bone or bone marrow

imaging, FDG-PET imaging, Gallium imaging, or labeled leukocyte imaging) is an

option in patients in whom diagnosis of periprosthetic joint infection has not been

established and are not scheduled for reoperation.

Strength of Recommendation: Limited

Description: Evidence from two or more “Low” strength studies with consistent findings, or

evidence from a single “Moderate” quality study recommending for or against the intervention or

diagnostic. A Limited recommendation means the quality of the supporting evidence that exists

is unconvincing, or that well-conducted studies show little clear advantage to one approach versus

another.

Implications: Practitioners should be cautious in deciding whether to follow a recommendation

classified as Limited, and should exercise judgment and be alert to emerging publications that

report evidence. Patient preference should have a substantial influencing role.

Rationale

The information presented throughout this guideline shows that there is no single

preoperative investigation that can reliably diagnose an infection. Diagnosis usually

depends on the combined use of numerous tests. Recognizing subclinical infections

before revision surgery is, therefore, a major concern.

Patients in whom diagnosis of infection has not been established includes patients with a

higher probability of infection who have abnormal ESR and/or CRP levels, but whose

aspiration results are inconclusive (i.e., fluid cannot be obtained from the joint or culture

and cell count results disagree).

The studies included for this recommendation, while of Level I and Level II quality, were

not specific to patients not scheduled for reoperation, so the work group downgraded the

strength of the recommendation from moderate to limited.

In addition, imaging studies may require special expertise and consultation with the

imaging provider.

Technetium-99- or Indium-111-labeled-Leukocyte Imaging

Four included studies indicated that a Tc-99-labeled white blood cell scan was possibly a

useful “rule in” test (range of positive LR:1.4-22),35, 93, 97, 101

while five included In-111

studies indicated that it was possibly useful as both a “rule in” and “rule out” test (range

of positive LR: 2-14; range of negative LR: 0.03-0.63).35, 46, 63, 85, 87

Combined labeled-Leukocyte/Bone Imaging


114

Three included studies of combined Tc-99 bone scans and In-111 white blood cell scans

also indicated the possible utility of these tests for confirming and excluding infection

(range of positive LR:3-18, range of negative LR: 0.12- 0.47).46, 95, 102

One study of

combined Tc-99 bone scans and Tc-99 white blood cell scans produced similar results

(positive LR: 6, negative LR: 0.44).84

Combined labeled-Leukocyte/Bone Marrow Imaging

The four included studies of combined leukocyte/bone marrow imaging indicated that the

test may be a good “rule in” and “rule out” test, but the results varied between studies

(range of positive LR: 9.8-45, range of negative LR: 0.02- 0.34).47, 60, 67, 97

Gallium-67 Imaging

Two included studies indicated that it may be a good “rule in” test but the ability of this

test to rule out infection was unclear (range of positive LR: 24-111, range of negative LR:

0.07-0.62).55, 88

FDG-PET Imaging

Three included studies of FDG-PET imaging indicated that the test is possibly good at

both ruling in and ruling out infection but, again, the results varied between studies

(range of positive LR: 11-19; range of negative LR: 0.16-0.66).15, 20, 60

Technetium-99m Bone Imaging

The three included studies of triple-phase Tc-99m bone scintigraphy varied in their

estimates of the test’s diagnostic efficacy, limiting the ability to determine whether the

test is effective at either confirming or excluding infection (range of positive LR: 2-8,

range of negative LR: 0.1-0.8).9, 58, 73

One included study of two-phase Tc-99m bone

scintigraphy provided no evidence of diagnostic efficacy (positive LR: 1.0, negative LR:

1.7).97

Based on these studies, triple-phase Tc-99m bone imaging may be possibly useful;

however, there is no consistent evidence of diagnostic benefit. Therefore more study is

needed.

Computed Tomography (CT) and Magnetic Resonance Imaging, MRI

Please refer to Recommendation 10 for information concerning these modalities.

Supporting Evidence

The indications for performing nuclear imaging varied between studies, and thus the

results presented here are not specific to patients not scheduled for reoperation. This

reduces the applicability of these studies’ findings and, hence, the strength of

recommendation.

Technetium-labeled leukocyte imaging: We included four studies: one study of mixed hip

and knee patients with reliable data (could separate out according to site but less than 25


115

knee patients), two studies of hip patients with moderately reliable data, and one study of

mixed patients with moderately reliable data.35, 93, 97, 101

Estimates of the positive

likelihood ratio ranged from 1.4-22, while estimates of the negative LR ranged from

0.06-0.52. Meta-analysis of these studies indicated between-study heterogeneity (I2 =

97%), limiting the ability to draw conclusions. The results are presented in Table 51.

Indium-labeled leukocyte imaging: We included five studies: one of hip patients, one of

knee patients, and three of mixed patients.35, 46, 63, 85, 87

All but one study contained

moderately reliable data. Meta-analysis of these studies indicated between-study

heterogeneity (I2 = 85%), as the positive likelihood ratio point estimates ranged from 2-

14 and the negative LR ranged from 0.03-0.63. The results are presented in Table 52.

Combined labeled-leukocyte/bone imaging: We included three Tc-99m HDP/In-111

leukocyte studies of mixed patients (could separate hip from knee patients in one) with

reliable data in one study and moderately reliable data in the other two.46, 95, 102

We also

included one Tc-99m MDP/Tc-99 leukocyte study of hip patients with moderately

reliable data.82

Each study found statistically significant results for positive and negative

likelihood ratios (range of positive LR:3-18, range of negative LR: 0.12- 0.47). Meta-

analysis of these four studies indicates small or moderate diagnostic effects (positive LR:

5.8, negative LR: 0.32). The results are presented in Table 53.

Combined labeled-leukocyte/bone marrow imaging: We included three studies of mixed

patients with reliable data in one study and moderately reliable data in the other two.47, 60,

97 We also included one study of hip patients with moderately reliable data.

67 Each study

found statistically significant results for positive and negative likelihood ratios (range of

positive LR: 9.8-45, range of negative LR: 0.02- 0.34). Meta-analysis of these studies

indicated between-study heterogeneity (I2 = 55%), limiting the ability to draw

conclusions. The results are presented in Table 54.

Gallium imaging: We included two studies with moderately reliable data.55, 88

Both

positive and negative likelihood ratios were statistically significant and suggest that

gallium imaging may be a good “rule in” test (range of positive LR: 24-111), but its

usefulness at ruling out infection is unclear (negative LR range: 0.07 – 0.62). The results

are presented in Table 55.

FDG-PET: We included one study of hip patients with reliable data and two studies of

mixed hip and knee patients with moderately reliable data.15, 20, 60

All three studies found

a statistically significant result for positive likelihood ratios, and two of the three found a

statistically significant result for negative likelihood ratios. The results are presented in

Table 56.

Tc-99m bone imaging: We included two studies of hip patients (one with reliable data,

one with moderately reliable data) and two studies of mixed hip and knee patients (both

with reliable data).9, 58, 73, 97

Three of the studies investigated triple-phase bone imaging, 9,

58, 73 while one investigated two-phase bone imaging.

97 For triple-phase bone imaging,

estimates of the positive likelihood ratio ranged from 2.3-8.5 and estimates of the

negative likelihood ratio ranged from 0.1-0.8, indicating possible, but inconsistent, small-


116

to-moderate diagnostic benefit. The two-phase bone imaging results (positive LR of 1.0

and a negative LR of 1.7) indicated a lack of diagnostic benefit. The results are presented

in Table 57.

Other imaging: We included one additional study with reliable data of antigranulocyte

antibody scintigraphy among knee patients53

and one study with moderately reliable data

of nanocolloid scintigraphy among hip patients.9 The diagnostic effects were significant

but with wide confidence intervals for both studies. The results are presented in Table 58.


117

SUMMARY OF EVIDENCE

Table 48. Nuclear Imaging Summary of Evidence

Test

Number

of

Studies

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity

(95% CI)

Tc-labeled WBC

imaging (range) 4 1.39 – 22.0 0.06 – 0.52 0.5 - 1 0.31 - 1

In-labeled WBC

imaging (range) 5 1.9 – 14.0 0.03 – 0.63 0.38 - 1 0.5 - 1

Combined bone/

labeled WBC

imaging 4

5.8

(3.1, 10.8)

0.32

(0.20, 0.50)

0.72

(0.59, 0.82)

0.88

(0.79, 0.93)

Combined bone

marrow/labeled

WBC imaging

(range)

4 9.8 – 45.5 0.02 – 0.34 0.67 - 1 0.91 – 1

Gallium imaging

(range) 2 24.4 -111 0.07 – 0.62 0.38 – 0.95 1

FDG-PET

imaging (range) 3 11.4 – 19.2 0.16 – 0.66 0.36 – 0.85 0.93 – 1

Triple-phase

bone imaging

(range) 3 2.33 – 8.53 0.13 - 0.78 0.33 – 0.88 0.76 – 0.90

Dual-phase bone

imaging 1 0.99

(0.94, 1.05)

1.72

(0.04, 84.59)

1

(0.88, 1)

0

(0, 0.07)

*Range presented when fewer than four studies or when meta-analysis indicated heterogeneity


118

EXCLUDED ARTICLES



Achong, et al.

1994

The computer-generated bone marrow subtraction image: a valuable adjunct to combined

In-111 WBC/Tc-99m in sulfur colloid scintigraphy for musculoskeletal infection

Not relevant - not

specific to pji

Aliabadi, et al.

1989 Cemented total hip prosthesis: radiographic and scintigraphic evaluation

Not best available

evidence

Bauer, et al.

1973 85Sr radionuclide scintimetry in infected total hip arthroplasty <25 patients/arm

Becker, et al.

1996 Rapid imaging of infections with a monoclonal antibody fragment (LeukoScan) <25 patients

Bernard, et al.

2004

Value of preoperative investigations in diagnosing prosthetic joint infection: retrospective

cohort study and literature review

Not best available

evidence

Boubaker, et al.

1995

Immunoscintigraphy with antigranulocyte monoclonal antibodies for the diagnosis of

septic loosening of hip prostheses

Not best available

evidence

Britton, et al.

1997 Clinical evaluation of technetium-99m infecton for the localisation of bacterial infection

Not relevant - not

specific to pji

Chacko, et al.

2003

Applications of fluorodeoxyglucose positron emission tomography in the diagnosis of

infection

Not best available

evidence

Chacko, et al.

2002

The importance of the location of fluorodeoxyglucose uptake in periprosthetic infection in

painful hip prostheses

Not best available

evidence

Chafetz, et al.

1985 Multinuclide digital subtraction imaging in symptomatic prosthetic joints

Not best available

evidence

Chik, et al.

1996

Tc-99m stannous colloid-labeled leukocyte scintigraphy in the evaluation of the painful

arthroplasty

Not best available

evidence


119



Crokaert, et al.

1982 Gallium-67 citrate as an aid to the diagnosis of infection in hip surgery <25 patients/arm

Dams, et al.

2000

99mTc-PEG liposomes for the scintigraphic detection of infection and inflammation:

clinical evaluation <25 patients

Datz, et al.

1994 The efficacy of indium-111-polyclonal IgG for the detection of infection and inflammation

Not relevant - not

specific to pji

Datz, et al.


Not relevant - not

specific to pji

de Lima Ramos, et al.

1996

Simultaneous administration of 99Tcm-HMPAO-labelled autologous leukocytes and

111In-labelled non-specific polyclonal human immunoglobulin G in bone and joint

infections

<25 patients

de Winter, et al.

2001

Fluorine-18 fluorodeoxyglucose-position emission tomography: a highly accurate imaging

modality for the diagnosis of chronic musculoskeletal infections <25 patients

Demirkol, et al.

1997 99Tc(m)-polyclonal IgG scintigraphy in the detection of infected hip and knee prostheses

Not best available

evidence

Devillers, et al.

1995

Technetium-99m hexamethylpropylene amine oxime leucocyte scintigraphy for the

diagnosis of bone and joint infections: a retrospective study in 116 patients

Not best available

evidence

El Esper, et al.

2004

The usefulness of 99mTc sulfur colloid bone marrow scintigraphy combined with 111In

leucocyte scintigraphy in prosthetic joint infection

Not best available

evidence

Feith, et al.

1976 Strontium 87mSr bone scanning for the evaluation of total hip replacement

Not relevant - not

specific to pji

Flivik, et al.

1993

Technetium-99m-nanocolloid scintigraphy in orthopedic infections: a comparison with

indium-111-labeled leukocytes <25 patients

Gomez-Luzuriaga, et

al. 1988 Scintigraphy with Tc, Ga and In in painful total hip prostheses <25 patients/arm


120



Hall, et al.

1998 Evaluation of the efficacy of 99mTc-Infecton, a novel agent for detecting sites of infection

Not relevant - not

specific to pji

Henderson, et al.

1996

The value of skeletal scintigraphy in predicting the need for revision surgery in total knee

replacement

Not best available

evidence

Itasaka, et al.


Not best available

evidence

Ivancevic, et al.

2002

Imaging of low-grade bone infection with a technetium-99m labelled monoclonal anti-

NCA-90 Fab' fragment in patients with previous joint surgery <25 patients

Iyengar, et al.

2005 Role of 99mTc Sulesomab in the diagnosis of prosthetic joint infections

Not best available

evidence

Jaruskova, et al.

2006 Role of FDG-PET and PET/CT in the diagnosis of prolonged febrile states

Not relevant - not

specific to pji

Jensen, et al.

1990 Tc-99m-MDP scintigraphy not informative in painful total hip arthroplasty

Not relevant - not

specific to pji

Larikka, et al.

2001

Improved method for detecting knee replacement infections based on extended combined

99mTc-white blood cell/bone imaging

Not best available

evidence

Larikka, et al.

2001

Extended combined 99mTc-white blood cell and bone imaging improves the diagnostic

accuracy in the detection of hip replacement infections

Not best available

evidence

Larikka, et al.

2002

Comparison of 99mTc ciprofloxacin, 99mTc white blood cell and three-phase bone

imaging in the diagnosis of hip prosthesis infections: improved diagnostic accuracy with

extended imaging time

Not best available

evidence

Li, et al.

1994

Bone scintigraphy of hip prostheses: Can analysis of patterns of abnormality improve

accuracy?

Not relevant - not

specific to pji

Lieberman, et al.

1993 Evaluation of painful hip arthroplasties. Are technetium bone scans necessary?

Not best available

evidence


121



Love, et al.

2001 Role of nuclear medicine in diagnosis of the infected joint replacement

Narrative review,


Manthey, et al.

2002

The use of [18 F]fluorodeoxyglucose positron emission tomography to differentiate

between synovitis, loosening and infection of hip and knee prostheses <25 patients

McInerney, et al.

1978 Technetium 99Tcm pyrophosphate scanning in the assessment of the painful hip prosthesis Insufficient Data

Merkel, et al.

1985

Comparison of indium-labeled-leukocyte imaging with sequential technetium-gallium

scanning in the diagnosis of low-grade musculoskeletal sepsis. A prospective study <25 patients

Merkel, et al.

1986

Sequential technetium-99m HMDP-gallium-67 citrate imaging for the evaluation of

infection in the painful prosthesis

>10% prostheses

already removed

Miles, et al.

1992

Scintigraphic abnormalities in patients with painful hip replacements treated

conservatively Insufficient Data

Moragas, et al.

1991 99Tcm-HMPAO leucocyte scintigraphy in the diagnosis of bone infection

Not best available

evidence

Mountford, et al.

1986 99Tcm-MDP, 67Ga-citrate and 111In-leucocytes for detecting prosthetic hip infection

Not best available

evidence

Mumme, et al.

2005

Diagnostic values of positron emission tomography versus triple-phase bone scan in hip

arthroplasty loosening Insufficient Data

Nijhof, et al.

1997 Hip and knee arthroplasty infection. In-111-IgG scintigraphy in 102 cases

Not best available

evidence

Nijhof, et al.

1997

Evaluation of infections of the locomotor system with indium-111-labeled human IgG

scintigraphy

Not best available

evidence

Ouzounian, et al.

1987 Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging <25 patients


122



Oyen, et al.

1991

Detection of subacute infectious foci with indium-111-labeled autologous leukocytes and

indium-111-labeled human nonspecific immunoglobulin G: a prospective comparative

study

Not relevant - not

specific to pji

Oyen, et al.

1990

Scintigraphic detection of bone and joint infections with indium-111-labeled nonspecific

polyclonal human immunoglobulin G

Not relevant - not

specific to pji

Oyen, et al.

1992

Diagnosis of bone, joint, and joint prosthesis infections with In-111-labeled nonspecific

human immunoglobulin G scintigraphy

Not best available

evidence

Pakos, et al.

2007

Prosthesis infection: diagnosis after total joint arthroplasty with antigranulocyte

scintigraphy with 99mTc-labeled monoclonal antibodies--a meta-analysis

Systematic review,


Pakos, et al.

2007

Use of (99m)Tc-sulesomab for the diagnosis of prosthesis infection after total joint

arthroplasty <25 patients

Palermo, et al.

1998

Comparison of technetium-99m-MDP, technetium-99m-WBC and technetium-99m-HIG

in musculoskeletal inflammation

Not relevant - not

specific to pji

Palestro, et al.

1990

Total-hip arthroplasty: periprosthetic indium-111-labeled leukocyte activity and

complementary technetium-99m-sulfur colloid imaging in suspected infection

Not best available

evidence

Palestro, et al.

1992

Diagnosis of musculoskeletal infection using combined In-111 labeled leukocyte and Tc-

99m SC marrow imaging

Not relevant - not

specific to pji

Palestro, et al.

1991

Infected knee prosthesis: diagnosis with In-111 leukocyte, Tc-99m sulfur colloid, and Tc-

99m MDP imaging

Not best available

evidence

Parvizi, et al.

2006 Periprosthetic infection: What are the diagnostic challenges?

Not best available

evidence

Pearlman, et al.

1980 The painful hip prosthesis: value of nuclear imaging in the diagnosis of late complications Insufficient Data

Pelosi, et al.

2004

99mTc-HMPAO-leukocyte scintigraphy in patients with symptomatic total hip or knee

arthroplasty: improved diagnostic accuracy by means of semiquantitative evaluation

Not best available

evidence


123



Pill, et al.

2006

Comparison of fluorodeoxyglucose positron emission tomography and (111)indium-white

blood cell imaging in the diagnosis of periprosthetic infection of the hip

Not best available

evidence

Prchal, et al.

1987 Detection of musculoskeletal infection with the indium-III leukocyte scan

Not relevant - not

specific to pji

Pring, et al.

1986 Indium-granulocyte scanning in the painful prosthetic joint Duplicate data

Reinartz, et al.

2009

FDG-PET in patients with painful hip and knee arthroplasty: technical breakthrough or just

more or the same

Systematic review,


Reinartz, et al.

2005

Radionuclide imaging of the painful hip arthroplasty: positron-emission tomography

versus triple-phase bone scanning

Not best available

evidence

Reuland, et al.

1991

Detection of infection in postoperative orthopedic patients with technetium-99m-labeled

monoclonal antibodies against granulocytes

Not relevant - not

specific to pji

Rosas, et al.

1998


joint replacement infection <25 patients per group

Rubello, et al.

1995 Three-phase bone scintigraphy pattern of loosening in uncemented hip prostheses

Not relevant - not

specific to pji

Rubello, et al.

2004

Role of anti-granulocyte Fab' fragment antibody scintigraphy (LeukoScan) in evaluating

bone infection: acquisition protocol, interpretation criteria and clinical results

Not relevant - not

specific to pji

Rubello, et al.

2008

Diagnosis of infected total knee arthroplasty with anti-granulocyte scintigraphy: the

importance of a dual-time acquisition protocol

Not best available

evidence

Rubin, et al.

1989 111In-labeled nonspecific immunoglobulin scanning in the detection of focal infection

Not relevant - not

specific to pji

Rushton, et al.

1982 The value of technetium and gallium scanning in assessing pain after total hip replacement

Not best available

evidence


124



Ryan,

2002 Leukoscan for orthopaedic imaging in clinical practice

Not best available

evidence

Sayle, et al.

1985 Indium-111 chloride imaging in the detection of infected prostheses <25 patients

Sciuk, et al.

1992

White blood cell scintigraphy with monoclonal antibodies in the study of the infected

endoprosthesis

Not best available

evidence

Serafini, et al.

1991

Clinical evaluation of a scintigraphic method for diagnosing inflammations/infections

using indium-111-labeled nonspecific IgG

Not relevant - not

specific to pji

Sfakianakis, et al.

1982

Comparisons of scintigraphy with In-111 leukocytes and Ga-67 in the diagnosis of occult

sepsis

Not relevant - not

specific to pji

Simonsen, et al.

2007

White blood cell scintigraphy for differentiation of infection and aseptic loosening: a

retrospective study of 76 painful hip prostheses

Not best available

evidence

Smith, et al.

2001

Radionuclide bone scintigraphy in the detection of significant complications after total

knee joint replacement

Not best available

evidence

Spinelli,

1976

The role of scintigraphy in the diagnosis of late complications of total prosthesis of the hip.

(Infection, loosening, ossification) Insufficient Data

Streule, et al.

1988

99Tcm-labelled HSA-nanocolloid versus 111In oxine-labelled granulocytes in detecting

skeletal septic process <25 eligible patients

Stumpe, et al.

2004

FDG PET for differentiation of infection and aseptic loosening in total hip replacements:

comparison with conventional radiography and three-phase bone scintigraphy

Not best available

evidence

Stumpe, et al.

2006 The value of FDG-PET in patients with painful total knee arthroplasty

Not best available

evidence

Taylor, et al.

1989

A simple method of identifying loosening or infection of hip prostheses in nuclear

medicine

Not best available

evidence

Tehranzadeh, et al.

1981 Radiological evaluation of painful total hip replacement

Not best available

evidence


125



Van Acker, et al.

2001

FDG-PET, 99mtc-HMPAO white blood cell SPET and bone scintigraphy in the evaluation

of painful total knee arthroplasties <25 patients

Vanquickenborne, et

al. 2003 The value of (18)FDG-PET for the detection of infected hip prosthesis <25 patients per arm

Vicente, et al.

2004

Diagnosis of orthopedic infection in clinical practice using Tc-99m sulesomab

(antigranulocyte monoclonal antibody fragment Fab'2)

Not best available

evidence

Vinjamuri, et al.

1996

Comparison of 99mTc infecton imaging with radiolabelled white-cell imaging in the

evaluation of bacterial infection

Not relevant - not

specific to pji

Virolainen, et al.


Not best available

evidence

von Rothenburg, et al.

2004

Imaging of infected total arthroplasty with Tc-99m-labeled antigranulocyte antibody

Fab'fragments

Not best available

evidence

Weiss, et al.

1979 99mTc-methylene diphosphonate bone imaging in the evaluation of total hip prostheses <25 patients/arm

Wellman, et al.

1988 Evaluation of metallic osseous implants with nuclear medicine Insufficient Data

Williams, et al.

1977

99Tcm-diphosphonate scanning as an aid to diagnosis of infection in total hip joint

replacements <25 patients/arm

Williams, et al.

1981 Gallium-67 scanning in the painful total hip replacement

Not best available

evidence

Wolf, et al.

2003

Localization and diagnosis of septic endoprosthesis infection by using 99mTc-HMPAO

labelled leucocytes

Not best available

evidence

Wukich, et al.

1987 Diagnosis of infection by preoperative scintigraphy with indium-labeled white blood cells

<25 patients with

prosthesis


126



Yapar, et al.

2001

The efficacy of technetium-99m ciprofloxacin (Infecton) imaging in suspected orthopaedic

infection: a comparison with sequential bone/gallium imaging <25 patients

Zhuang, et al.

2002 Persistent non-specific FDG uptake on PET imaging following hip arthroplasty <25 patients

Zhuang, et al.

2001 The promising role of 18F-FDG PET in detecting infected lower limb prosthesis implants

Not best available

evidence

Zoccali, et al.

2009

The role of FDG-PET in distinguishing between septic and aseptic loosening in hip

prosthesis: a review of literature

Systematic review,



127

STUDY QUALITY

Table 50. Nuclear Imaging - Quality

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Nagoya 46 3-phase bone scintigraphy I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Klett 28 antigranulocyte antibody BW 250/183

scintigraphy I ? ● ● ● ● ● ● ● ● ● ● ● ● ●

Glithero 25 In-111 leukocyte scan I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Joseph 36 In-111 leukocyte/Tc-99m sulfur colloid

scans I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Joseph 58 In -111 leukocyte/Tc-99m sulfur colloid

scans I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Joseph 36

In -111 leukocyte/Tc-99m sulfur colloid

scans and with blood pooling and flow

phase data

I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Joseph 58

In -111 leukocyte/Tc-99m sulfur colloid

scans and with blood pooling and flow

phase data

I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Glithero 31 Tc-99m HMPAO leukocyte scintigraphy I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Glithero 45 Tc-99m HMPAO or In-111-oxine

leukocyte scan I ● ● ● ● ● ● ● ● ● ● ● ● ● ●


128

Table 50. Nuclear Imaging – Quality (Continued)

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Glithero 56 Tc-99m HMPAO or In-111-oxine

leukocyte scan I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Teller 166 Tc-99m HPD/In-111 leukocyte scan I ? ● ● ● ● ● ● ● ● ● ? ● ● ●

Reing 79 Ga-67 scan II ? ○ ● ● ● ● ● ● ○ ● ● ● ● ●

Pring 40 In-111 granulocyte scan II ? ○ ● ● ● ● ● ● ● ● ? ● ● ●

Mulamba 30 In-111 leukocyte/sulfur colloid scan II ? ○ ● ● ● ● ● ● ○ ● ● ● ● ●

Rand 38 In-111 leukocyte scan II ● ○ ● ● ● ● ● ● ● ● ? ● ● ●

Magnuson 98 In-111 leukocyte scan II ? ○ ● ● ● ● ● ● ? ● ? ● ● ●

Johnson 29 In-111 leukocyte scan II ● ● ● ● ● ● ● ● ○ ● ● ● ● ●

Kraemer 33 sequential scan and aspiration II ? ? ● ● ● ● ● ? ○ ● ● ● ● ●

Kraemer 43 sequential Tc-99m bone scan/Ga-67

scan II ? ? ● ● ● ● ● ? ○ ● ● ● ● ●

Johnson 29 Tc-99m HDP/In-111 leukocyte scan II ● ● ● ● ● ● ● ● ○ ● ● ● ● ●


129


● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Scher 91

Tc-99m HDP/indium-111-labeled

leukocyte scan (positive if incongruent

scans)

II ? ○ ● ● ● ● ● ● ● ● ? ● ● ●

Scher 40

Tc-99m HDP/indium-111-labeled

leukocyte scan (positive if incongruent

scans)

II ? ○ ● ● ● ● ● ● ● ● ? ● ● ●

Savarino 26 Tc-99m –HMPAO scan II ● ● ● ● ● ● ● ○ ● ● ● ● ● ○

Savarino 26 Tc-99m –HMPAO scan II ● ● ● ● ● ● ● ○ ● ? ? ● ● ○

Savarino 26 Tc-99m –HMPAO scan II ● ● ● ● ● ● ● ○ ● ? ? ● ● ○

Benitez

Segura 77

Tc-99m HMPAO leukocyte

scintigraphy II ● ● ● ● ● ● ● ● ○ ● ● ● ● ●

Benitez

Segura 77

Tc-99m HMPAO leukocyte/Tc-99m

stannous microcolloid bone marrow

scan

II ● ● ● ● ● ● ● ● ○ ● ● ● ● ●

Benitez

Segura 77

Tc-99m HMPAO leukocyte/Tc-99m

stannous microcolloid bone marrow

scan/Tc-99m MDP bone scan

II ● ● ● ● ● ● ● ● ○ ● ● ● ● ●

Benitez

Segura 77 Tc-99m MDP bone scan II ● ● ● ● ● ● ● ● ○ ● ● ● ● ●


130


● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Bernay 31 Tc-99m MDP scintigraphy II ● ● ? ● ● ● ● ○ ● ● ? ● ● ●

Levitsky 58 Tc-99m MDP TPBI II ● ? ● ● ● ● ● ● ● ● ● ? ● ○

Levitsky 54 Tc-99m MDP TPBI and plain

radiographs II ● ? ● ● ● ● ● ? ● ● ● ? ● ○

Pons 78

Tc-99m MDP, Tc-99 HmPAO white

blood cells scintigraphy (positive if

areas of increased isotope uptake for

Tc were congruent with high levels of

white blood cell labelled with Tc)

II ● ○ ● ● ● ● ● ● ○ ● ? ? ● ●

Bernay 31 Tc-99m nanocolloid scintigraphy II ● ● ? ● ● ● ● ○ ● ● ? ● ● ●

Sudanese 35 Tc-99m-labelled granulocyte bone

scan II ? ? ● ● ● ● ● ● ○ ● ● ● ● ●

Love 59 WBC/marrow imaging II ? ● ● ● ● ● ● ● ○ ● ? ● ● ●

Chryssikos 127 FDG-PET - increased FDG uptake at

prosthesis-bone interface I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Delank 27 FDG-PET - FDG uptake in the

periprosthetic soft tissue II ● ● ? ● ● ● ● ● ○ ● ? ● ● ●


131


● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Love 59

FDG-PET - activity at bone-prosthesis

interface (of femoral component for

hip, femoral or tibial for knee)

II ? ● ● ● ● ● ● ● ○ ● ? ● ● ●

Love 59 FDG-PET - any periprosthetic activity II ? ● ● ● ● ● ● ● ○ ● ? ● ● ●

Love 59

FDG-PET - semiquantitative analysis

of bone-prostesis interface activity

(target-background ratio)

II ? ● ● ● ● ● ● ● ○ ● ? ● ● ●

Love 59

FDG-PET/WBC marrow - any

perisprosthetic activity on FDG image

without corresponding activity on

marrow image

II ? ● ● ● ● ● ● ● ○ ● ? ● ● ●


132

STUDY RESULTS

Figure 13. Technetium-labeled-Leukocyte Imaging Results – Likelihood Ratios

StudyId

Glithero - Hip - Tc or In

Savarino

Sudanese

Glithero - Hip and Knee - Tc only

Glithero - Hip and Knee - Tc or In

Benitez Segura

101 2 5

DLR POSITIVE

StudyId

Glithero - Hip - Tc or In

Savarino

Sudanese

Glithero - Hip and Knee - Tc only

Glithero - Hip and Knee - Tc or In

Benitez Segura

1.1 .2 .5

DLR NEGATIVE


133

Figure 14. Indium-labeled-Leukocyte Imaging Results - Likelihood Ratios

StudyId

Glithero

Rand

Magnuson

Johnson

Pring

10521

DLR POSITIVE

StudyId

Glithero

Rand

Magnuson

Johnson

Pring

1.1 .2 .5

DLR NEGATIVE

Figure 15. Combined Leukocyte/Bone Imaging Results – Likelihood Ratios

StudyId

COMBINED

Teller

Johnson

Scher

Pons

1 2 5 10

DLR POSITIVE

StudyId

COMBINED

Teller

Johnson

Scher

Pons

0 .1 .2 .5 1

DLR NEGATIVE


134

Figure 16. Combined Leukocyte/Bone Marrow Imaging Results - Likelihood Ratios

StudyId

Love

Benitez Segura

Mulamba

Joseph - Hip & Knee with phase data

Joseph - Hip & Knee

Joseph - Hip with phase data

Joseph - Hip

101 2 5

DLR POSITIVE

StudyId

Love

Benitez Segura

Mulamba

Joseph - Hip & Knee with phase data

Joseph - Hip & Knee

Joseph - Hip with phase data

Joseph - Hip

1.1 .2 .5

DLR NEGATIVE

Figure 17. FDG-PET Imaging Results - Likelihood Ratios

StudyId

Love - FDG-PET/WBC marrow

Love - semiquantitative analysis of BPI activity

Love - any periprosthetic activity

Love - activity at BPI

Delank - uptake in the periprosthetic soft tissue

Chryssikos - increased uptake at BPI

1 2 5 10

DLR POSITIVE

StudyId

Love - FDG-PET/WBC marrow

Love - semiquantitative analysis of BPI activity

Love - any periprosthetic activity

Love - activity at BPI

Delank - uptake in the periprosthetic soft tissue

Chryssikos - increased uptake at BPI

1.1 .2 .5

DLR NEGATIVE


135

Figure 18. Technetium-99m Bone Imaging Results - Likelihood Ratios

StudyId

Nagoya

Bernay

Benitez Segura

Levitsky

1 2 5 10

DLR POSITIVE

StudyId

Nagoya

Bernay

Benitez Segura

Levitsky

.1.2 .5 1

DLR NEGATIVE

*Benitez Segura used 2-phase rather than 3-phase bone imaging


136

Figure 19. Other Nuclear Imaging Results - Likelihood Ratios

StudyId

Bernay - nanocolloid scintigraphy

Klett - antibody BW 250/183 scintigraphy

Kraemer - Sequential scan or aspiration

Kraemer - Sequential bone/Ga-67 scan

Reing - Ga-67 scan

1 2 510

DLR POSITIVE

StudyId

Bernay - nanocolloid scintigraphy

Klett - antibody BW 250/183 scintigraphy

Kraemer - Sequential scan or aspiration

Kraemer - Sequential bone/Ga-67 scan

Reing - Ga-67 scan

.1 .2 .5 1

DLR NEGATIVE


137

Table 51. Technetium-99m-labeled-Leukocyte Imaging

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Glithero 45

Tc-99m

HMPAO or

In-111-

oxine

leukocyte

scan

Intraoperative

cultures Hip

16.5

(0.91,

298.82)

0.76

(0.56,

1.03)

0.23

(0.05,

0.54)

1

(0.89, 1) 3 0 10 32

II Savarino 26

Tc-99m-

HMPAO

granulocyte

scintigraphy

Intraoperative

cultures Hip

7.12

(0.44,

116.34)

0.71

(0.5, 1.01)

0.31

(0.11,

0.59)

1

(0.69, 1) 5 0 11 10

II Savarino 26

Tc-99m-

HMPAO

granulocyte

scintigraphy

Histology Hip

12.69

(0.77,

208.34)

0.6

(0.37,

0.96)

0.42

(0.15,

0.72)

1

(0.77, 1) 5 0 7 14

II Savarino 26

Tc-99m-

HMPAO

granulocyte

scintigraphy

Intraoperative

cultures and

histology

Hip

17

(1.04,

277.87)

0.52

(0.28,

0.94)

0.5

(0.19,

0.81)

1

(0.79, 1) 5 0 5 16

II Sudanese 35

Tc-99m

granulocyte

bone scan

Intraoperative

cultures Hip

7.56

(2.8,

20.39)

0.06

(0, 0.94)

1

(0.63, 1)

0.89

(0.71,

0.98)

8 3 0 24


138

Table 51. Technetium-99m-labeled-Leukocyte Imaging (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Glithero 31

Tc-99m

HMPAO

leukocyte

scintigraphy

Intraoperative

cultures

Mixed

(20

hip,

11

knee)

22

(1.33,

362.92)

0.51

(0.28,

0.93)

0.5

(0.19,

0.81)

1

(0.84, 1) 5 0 5 21

I Glithero 56

Tc-99m

HMPAO or

In-111-

oxine

leukocyte

scan

Intraoperative

cultures

Mixed

(45

hip,

11

knee)

34.89

(2.12,

573.23)

0.56

(0.37,

0.84)

0.44

(0.22,

0.69)

1

(0.91, 1) 8 0 10 38

II Benitez

Segura 77

Tc-99m

HMPAO

leukocyte

scintigraphy

Intraoperative

cultures

Mixed

(48

hip,

29

knee)

1.39

(1.14, 1.7)

0.12

(0.02,

0.84)

0.96

(0.82, 1)

0.31

(0.18,

0.45)

27 34 1 15


139

Table 52. Indium-111-labeled-Leukocyte Imaging

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Glithero 25

In-111

leukocyte

scan

Intraoperative

cultures Hip

14

(0.81,

242.78)

0.63

(0.37, 1.06)

0.38

(0.09,

0.76)

1

(0.8, 1) 3 0 5 17

II Rand 38

In-111

leukocyte

scan

at least 2 of:

1)positive

culture results

2)acute

inflammatory

histologic

findings

3)clinical

sepsis with pus

within the joint

Knee

5.56

(1.92,

16.09)

0.2

(0.07, 0.56)

0.83

(0.59,

0.96)

0.85

(0.62,

0.97)

15 3 3 17

II Magnuson 98

In-111

leukocyte

scan

Intraoperative

cultures or

histology

Mixed 3.25

(2.02, 5.23)

0.16

(0.08, 0.36)

0.88

(0.76,

0.95)

0.73

(0.58,

0.85)

44 13 6 35

II Johnson 29

In-111

leukocyte

scan

Intraoperative

cultures Mixed

1.9

(1.21, 2.98)

0.1

(0.01, 1.54)

1

(0.66, 1)

0.5

(0.27,

0.73)

9 10 0 10

II Pring 40

In-111

granulocyte

scan

Intraoperative

cultures or

histology or

deep abscess

Mixed

8.96

(2.77,

28.94)

0.03

(0, 0.46)

1

(0.81, 1)

0.91

(0.71,

0.99)

18 2 0 20


140

Table 53. Combined Leukocyte/Bone Imaging

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


II Pons 78

Tc-99m

MDP, Tc-99

HMPAO

leukocyte

scintigraphy

Intraoperative

cultures and

histology

Hip

6.3

(2.65,

14.98)

0.44

(0.24, 0.83)

0.6

(0.32,

0.84)

0.9

(0.8, 0.96) 9 6 6 57

II Scher 91*

Tc-99m

HDP/In-111

leukocyte

scan

At least 2 of:

1)positive

intraoperative

cultures (either

broth or plate)

2)intraoperative

findings of gross

purulence within

the joint 3)final

permanent

histologic section

incidcating acute

inflammation

based on ≥10

PMN/HPF in 5

areas

Hip

8.1

(3.22,

20.35)

0.43

(0.2, 0.93)

0.6

(0.26,

0.88)

0.93

(0.85,

0.97)

6 6 4 75


141

Table 53. Combined Leukocyte/Bone Imaging (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


II Scher 40*

Tc-99m

HDP/In-

111

leukocyte

scan

At least 2 of:

1)positive

intraoperative

cultures (either

broth or plate)

2)intraoperative

findings of gross

purulence within

the joint 3)final

permanent

histologic section

incidcating acute

inflammation

based on ≥10

PMN/HPF in 5

areas

Knee 4.06

(1.83, 8.98)

0.15

(0.04, 0.56)

0.88

(0.64,

0.99)

0.78

(0.56,

0.93)

15 5 2 18

I Teller 166

Tc-99m

HPD/In-

111

leukocyte

scan

Intraoperative

cultures of frank

purulence

Mixed 2.86

(1.85, 4.44)

0.47

(0.27, 0.82)

0.64

(0.41,

0.83)

0.78

(0.7, 0.84) 14 32 8 112

II Johnson 29

Tc-99m

HDP/In-

111

leukocyte

scan

Intraoperative

cultures Mixed

17.78

(2.6,

121.78)

0.12

(0.02, 0.74)

0.89

(0.52, 1)

0.95

(0.75, 1) 8 1 1 19

*Three hip scans and one knee scan regarded as equivocal were excluded from the analysis


142

Table 54. Combined Leukocyte/Bone Marrow Imaging

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Joseph 36

In-111

leukocyte/Tc-

99m sulfur

colloid scans

at least 2 of:

1)positive

intraoperative

culture 2)final

histology (>10

PMN/HPF in 5

areas)

3)intraoperative

findings of gross

purulence within

the joint

Hip

19.6

(1.11,

347.03)

0.66

(0.42, 1.05)

0.33

(0.07, 0.7)

1

(0.87, 1) 3 0 6 27

I Joseph 36

In-111

leukocyte/Tc-

99m sulfur

colloid scans

and with

blood pooling

and flow

phase data

at least 2 of:

1)positive

intraoperative

culture 2)final

histology (>10

PMN/HPF in 5

areas)

3)intraoperative

findings of gross

purulence within

the joint

Hip

30.8

(1.87,

508.31)

0.46

(0.23, 0.91)

0.56

(0.21,

0.86)

1

(0.87, 1) 5 0 4 27


143

Table 54. Combined Leukoycte/Bone Marrow Imaging (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Joseph 58

In-111

leukocyte/Tc-

99m sulfur

colloid scans

at least 2 of:

1)positive

intraoperative

culture 2)final

histology (>10

PMN/HPF in 5

areas)

3)intraoperative

findings of

gross purulence

within the joint

Mixed

(36

hip,

22

knee)

41.25

(2.5,

681.7)

0.54

(0.34,

0.85)

0.47

(0.21,

0.73)

1

(0.92, 1) 7 0 8 43

I Joseph 58

In-111

leukocyte/Tc-

99m sulfur

colloid scans

and with

blood pooling

and flow

phase data

at least 2 of:

1)positive

intraoperative

culture 2)final

histology (>10

PMN/HPF in 5

areas)

3)intraoperative

findings of

gross purulence

within the joint

Mixed

(36

hip,

22

knee)

28.67

(4, 205.52)

0.34

(0.17, 0.7)

0.67

(0.38,

0.88)

0.98

(0.88, 1) 10 1 5 42

II Mulamba 30

In-111

leukocyte/Tc-

99m sulfur

colloid scans

Intraoperative

cultures Hip

32.14

(2.08,

497.33)

0.11

(0.02, 0.5)

0.92

(0.64, 1)

1

(0.8, 1) 12 0 1 17


144

Table 54. Combined Leukoycte/Bone Marrow Imaging (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


II Benitez

Segura 77

Tc-99m

HMPAO

leukocyte/Tc-

99m stannous

microcolloid

bone marrow

scan

Intraoperative

cultures

Mixed

(48

hip,

29

knee)

45.5

(6.52,

317.44)

0.07

(0.02,

0.28)

0.93

(0.76,

0.99)

0.98

(0.89, 1) 26 1 2 48

II Benitez

Segura 77

Tc-99m

HMPAO

leukocyte/Tc-

99m stannous

microcolloid

bone marrow

scan/Tc-99m

MDP bone

scan

Intraoperative

cultures

Mixed

(48

hip,

29

knee)

45.5

(6.52,

317.44)

0.07

(0.02,

0.28)

0.93

(0.76,

0.99)

0.98

(0.89, 1) 26 1 2 48

II Love 59

In-111

leukocyte/Tc-

99m sulfur

colloid scans

Intraoperative

cultures or

histology

Mixed

(40

hip,

19

knee)

9.81

(3.62,

26.54)

0.02

(0, 0.33)

1

(0.86, 1)

0.91

(0.76,

0.98)

25 3 0 31


145

Table 55. Gallium-67 Imaging

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


II Reing 79 Ga-67

scan

Intraoperative

cultures

Mixed

(67

hips,

12

knee, 1

elbow)

111

(7.0, 1765)

0.07

(0.02, 0.34)

0.95

(0.75, 1)

1

(0.94, 1) 19 0 1 59

II Kraemer 43

Sequential

Tc-99m

bone

scan/Ga-

67 scan

Intraoperative

cultures Hip

24.36

(1.44, 410)

0.62

(0.4, 0.94)

0.38

(0.14,

0.68)

1

(0.88, 1) 5 0 8 30

II Kraemer 33

Sequential

scan or

aspiration

Intraoperative

cultures Hip

14

(1.96, 100)

0.38

(0.17, 0.84)

0.64

(0.31,

0.89)

0.95

(0.77, 1) 7 1 4 21


146

Table 56. FDG-PET Imaging

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Chryssikos 127

FDG-PET -

increased

FDG uptake

at prosthesis-

bone

interface

At least 1 of: 1)an

open wound or

sinus

communicating

with the joint 2)

systemic infection

with pain in the hip

and purulent fluid

within the joint

3)positive result on

at least 3 tests

(ESR, CRP, joint

aspiration,

intraoperative

frozen section, and

intraoperative

culture)

Hip

11.39

(5.51,

23.58)

0.16

(0.07, 0.37)

0.85

(0.68,

0.95)

0.93

(0.85,

0.97)

28 7 5 87

II Delank 27

FDG-PET -

FDG uptake

in the

periprosthetic

soft tissue

Intraoperative

Macroscopic,

Microbiological,

and

Histopathological

examinations

Mixed

(22

hip, 5

knee)

19.17

(1.05, 348)

0.6

(0.3, 1.18)

0.4

(0.05,

0.85)

1

(0.85, 1) 2 0 3 22


147

Table 56. FDG-PET Imaging (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio (95%

CI)

Sensitivity

(95% CI)

Specificity


II Love 59

FDG-PET - activity

at bone-prosthesis

interface

Intraoperative

cultures or

histology

Mixed

(40

hip, 19

knee)

0.93

(0.58, 1.5)

1.09

(0.62, 1.9)

0.52

(0.31,

0.72)

0.44

(0.27,

0.62)

13 19 12 15

II Love 59

FDG-PET - any

periprosthetic

activity

Intraoperative

cultures or

histology

Mixed

(40

hip, 19

knee)

1.09

(0.96, 1.23)

0.19

(0.01, 3.56)

1

(0.86, 1)

0.09

(0.02,

0.24)

25 31 0 3

II Love 59

FDG-PET -

semiquantitative

analysis of bone-

prosthesis interface

activity (target-

background ratio)

Intraoperative

cultures or

histology

Mixed

(40

hip, 19

knee)

12.24

(1.66, 90.5)

0.66

(0.49, 0.89)

0.36

(0.18,

0.57)

0.97

(0.85, 1) 9 1 16 33

II Love 59

FDG-PET/WBC

marrow - any

perisprosthetic

activity on FDG

image without

corresponding

activity on marrow

image

Intraoperative

cultures or

histology

Mixed

(40

hip, 19

knee)

1.48

(1.14, 1.93)

0.11

(0.02, 0.82)

0.96

(0.8, 1)

0.35

(0.2, 0.54) 24 22 1 12


148

Table 57. Technetium-99m Bone Imaging

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Nagoya 46

Tc-99m 3-

phase bone

scintigraphy

at least 1 of:

1)intraoperative

or open biopsy

tissue culture,

2)histology,

3)visibly

purulent

synovial fluid

Hip

8.53

(2.88,

25.25)

0.13

(0.04, 0.49)

0.88

(0.64,

0.99)

0.9

(0.73,

0.98)

15 3 2 26

II Bernay 31

Tc-99m

MDP 3-

phase

scintigraphy

Pathological

and gross

operative

findings

Hip

3.36

(1.47,

7.67)

0.26

(0.07, 0.93)

0.8

(0.44,

0.97)

0.76

(0.53,

0.92)

8 5 2 16

II Benitez

Segura 77

Tc-99m

MDP 2-

phase bone

scintigraphy

Intraoperative

cultures

Mixed

(48

hip,

29

knee)

0.99

(0.94,

1.05)

1.72

(0.04,

84.59)

1

(0.88, 1)

0

(0, 0.07) 28 49 0 0

II Levitsky 58*

Tc-99m

MDP 3-

phase bone

scintigraphy

Intraoperative

cultures and

gross sepsis

Mixed

(63

hip, 9

knee)

2.33

(0.74,

7.37)

0.78

(0.48, 1.25)

0.33

(0.07, 0.7)

0.86

(0.73,

0.94)

3 7 6 42

II Levitsky 54*

Tc-99m

MDP 3-

phase bone

scintigraphy

and plain

radiographs

Intraoperative

cultures and

gross sepsis

Mixed

(63

hip, 9

knee)

4.31

(1.18,

15.75)

0.68

(0.4, 1.18)

0.38

(0.09,

0.76)

0.91

(0.79,

0.98)

3 4 5 42

*Analysis excludes 14 indeterminate results (positive cultures or sepsis, but not both)


149

Table 58. Other Nuclear Imaging tests

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Klett 28

Antigranulocyte

antibody BW

250/183

scintigraphy

Histology Knee

4.41

(1.74,

11.19)

0.05

(0, 0.7)

1

(0.75, 1)

0.8

(0.52,

0.96)

13 3 0 12

II Bernay 31

Tc-99m

nanocolloid

scintigraphy

Pathological

and gross

operative

findings

Hip

6

(2.28,

15.82)

0.05

(0, 0.82)

1

(0.69, 1)

0.86

(0.64,

0.97)

10 3 0 18


150

RECOMMENDATION 10 We are unable to recommend for or against computed tomography (CT) or magnetic

resonance imaging (MRI) as a diagnostic test for periprosthetic joint infection.

Strength of Recommendation: Inconclusive

Description: Evidence from a single low quality study or conflicting findings that do not allow a

recommendation for or against the intervention. An Inconclusive recommendation means that

there is a lack of compelling evidence resulting in an unclear balance between benefits and

potential harm.

Implications: Practitioners should feel little constraint in deciding whether to follow a

recommendation labeled as Inconclusive and should exercise judgment and be alert to future

publications that clarify existing evidence for determining balance of benefits versus potential

harm. Patient preference should have a substantial influencing role.

Rationale

Computed Tomography (CT)

One included study indicated that some CT findings are possibly useful in the diagnosis

of periprosthetic infection, but more study is needed (range of positive LR: 0.3-46; range

of negative LR: 0.04-1.3).19

The evidence indicates that CT may be a good “rule in” test

but not as good a “rule out” test. This evidence is insufficient and does not allow a

recommendation for or against the use of this modality.

Magnetic Resonance Imaging (MRI)

There is insufficient evidence to address the diagnostic efficacy of MRI for diagnosing

periprosthetic infections. Based on the lack of evidence, we cannot recommend for or

against the use of MRI.

Supporting Evidence

CT: We included one study of hip patients with reliable data which examined computed

tomography (CT).19

Of the findings on CT that were studied, fluid collections in muscles

and perimuscular fat, joint distention, and soft-tissue abnormalities each produced

statistically significant positive and negative likelihood ratios. Findings of periostitis and

fluid-filled bursae each produced a statistically significant positive likelihood ratio. The

other findings did not produce statistically significant results. The results are presented in

Table 62.

No MRI studies met the inclusion criteria for this recommendation.

SUMMARY OF EVIDENCE

Table 59. CT and MRI Summary of Evidence

Test Number Positive Negative Sensitivity Specificity


151

of

Studies

Likelihood

Ratio

(95% CI)

Likelihood

Ratio

(95% CI)

(95% CI) (95% CI)

CT imaging –

various measures

(range) 1 0.29 – 45.7 0.04 – 1.28 0.08 - 1 0.3 - 1

EXCLUDED ARTICLES


Author Title Reason for

Exclusion

Cooper, et al.

2008

Magnetic Resonance Imaging in the Diagnosis and

Management of Hip Pain After Total Hip Arthroplasty <25 patients

Reinus, et al.

1996

Evaluation of femoral prosthetic loosening using CT

imaging <25 patients

Sofka, et al.

2003 Magnetic resonance imaging of total knee arthroplasty

Insufficient

Data


152

STUDY QUALITY

Table 61. Study Quality - CT

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Cyteval 65

CT -

asymmetric

position of

femoral head

I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Cyteval 65

CT - bone

abnormalities

(focal or

nonfocal low

attenuation,

periostitis)

I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Cyteval 65

CT - fluid

collections in

muscles and

perimuscular

fat

I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Cyteval 65 CT - fluid-

filled bursae I ● ● ● ● ● ● ● ● ● ● ● ● ● ●


153

Table 61. Study Quality – CT (Continued)

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Cyteval 65

CT - fluid-

filled bursae -

greater

trochanter

I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Cyteval 65

CT - fluid-

filled bursae -

iliopsoas

I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Cyteval 65 CT - focal low

attenuation I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Cyteval 65 CT - joint

distention I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Cyteval 65

CT - nonfocal

low

attenuation

I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Cyteval 65 CT - periostitis I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Cyteval 65

CT - soft-

tissue

abnormalities

I ● ● ● ● ● ● ● ● ● ● ● ● ● ●


154

STUDY RESULTS

Figure 20. CT Imaging Results - Likelihood Ratios

StudyId

Cyteval - fluid bursae - iliopsoas

Cyteval - fluid bursae - greater trochanter

Cyteval - fluid-filled bursae

Cyteval - fluid collections


Cyteval - soft-tissue abnormalities

Cyteval - joint distention

Cyteval - nonfocal low attenuation

Cyteval - focal low attenuation



1 2 510

DLR POSITIVE

StudyId

Cyteval - fluid bursae - iliopsoas

Cyteval - fluid bursae - greater trochanter

Cyteval - fluid-filled bursae

Cyteval - fluid collections


Cyteval - soft-tissue abnormalities

Cyteval - joint distention

Cyteval - nonfocal low attenuation

Cyteval - focal low attenuation



0 .1 .2 .5 1

DLR NEGATIVE


155

Table 62. CT Imaging

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Cyteval 65

CT -

asymmetric

position of

femoral head

Intraoperative

Cultures (≥2) Hip

0.29

(0.04, 2.02)

1.28

(1.01, 1.63)

0.08

(0, 0.38)

0.72

(0.58, 0.83) 1 15 11 38

I Cyteval 65 CT -

periostitis

Intraoperative

Cultures (≥2) Hip

20.77

(1.06, 407)

0.82

(0.62, 1.06)

0.17

(0.02, 0.48)

1

(0.93, 1) 2 0 10 53

I Cyteval 65

CT - fluid-

filled bursae

- iliopsoas

Intraoperative

Cultures (≥2) Hip

2.65

(0.73, 9.6)

0.83

(0.59, 1.16)

0.25

(0.05, 0.57)

0.91

(0.79, 0.97) 3 5 9 48

I Cyteval 65

CT - focal

low

attenuation

Intraoperative

Cultures (≥2) Hip

1.47

(0.57, 3.78)

0.86

(0.56, 1.32)

0.33

(0.1, 0.65)

0.77

(0.64, 0.88) 4 12 8 41

I Cyteval 65

CT - fluid-

filled bursae

- greater

trochanter

Intraoperative

Cultures (≥2) Hip

17.67

(2.16, 144)

0.68

(0.45, 1.02)

0.33

(0.1, 0.65)

0.98

(0.9, 1) 4 1 8 52

I Cyteval 65

CT -

nonfocal low

attenuation

Intraoperative

Cultures (≥2) Hip

0.88

(0.43, 1.83)

1.1

(0.64, 1.9)

0.42

(0.15, 0.72)

0.53

(0.39, 0.67) 5 25 7 28

I Cyteval 65 CT - fluid-

filled bursae

Intraoperative

Cultures (≥2) Hip

3.68

(1.34,

10.08)

0.66

(0.4, 1.07)

0.42

(0.15, 0.72)

0.89

(0.77, 0.96) 5 6 7 47


156

Table 62. CT Imaging (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Cyteval 65

CT - fluid

collections in

muscles and

perimuscular

fat

Intraoperative

Cultures (≥2) Hip

45.69

(2.69, 775)

0.58

(0.37, 0.93)

0.42

(0.15,

0.72)

1

(0.93, 1) 5 0 7 53

I Cyteval 65 CT - bone

abnormalities

Intraoperative

Cultures (≥2) Hip

1.07

(0.74, 1.56)

0.83

(0.29, 2.4)

0.75

(0.43,

0.95)

0.3

(0.18,

0.44)

9 37 3 16

I Cyteval 65 CT - joint

distention

Intraoperative

Cultures (≥2) Hip

22.08

(5.54,

88.03)

0.17

(0.05, 0.61)

0.83

(0.52,

0.98)

0.96

(0.87, 1) 10 2 2 51

I Cyteval 65

CT - soft-

tissue

abnormalities

Intraoperative

Cultures (≥2) Hip

6.92

(3.53,

13.57)

0.04

(0, 0.68)

1

(0.74, 1)

0.87

(0.75,

0.95)

12 7 0 46


157

RECOMMENDATION 11 We recommend against the use of intraoperative Gram stain to rule out periprosthetic

joint infection.









Rationale

Our systematic review included three studies of Gram stain in the diagnosis of

periprosthetic joint infection.3, 78, 100

Negative likelihood ratios suggest this is not a good

“rule out” test (values >0.5). Comparatively, negative likelihood ratios for synovial fluid

white blood cell count and differential tests (Recommendation 4) are much lower (<0.1).

Thus, Gram stain is not a useful test for ruling out periprosthetic infection.

Supporting Evidence

Three included studies addressed the diagnostic utility of intraoperative Gram stains (one

hip, one knee, one hip and knee).3, 78, 100

Data from the knee study were of moderate

reliability, while the data from the other two studies were reliable. The test is fairly good

at ruling in infection (positive likelihood ratios greater than 10) but not as good at ruling

out infection (negative likelihood ratios greater than 0.5). Results are summarized in

Table 63.

SUMMARY OF EVIDENCE

Table 63. Gram Stain Summary of Evidence

Test Number

of Studies

Positive

Likelihood

Ratio (95%

CI)

Negative

Likelihood

Ratio (95%

CI)

Sensitivity

(95% CI)

Specificity

(95% CI)

Gram Stain

(range) 3 10.8 – 42.3 0.56 – 0.83 0.19 – 0.44 0.97 -1

*Range presented because fewer than four studies


158

EXCLUDED ARTICLES



Atkins, et al.

1998

Prospective evaluation of criteria for microbiological diagnosis of prosthetic-joint infection

at revision arthroplasty. The OSIRIS Collaborative Study Group

Not best available

evidence

Barrack, et al.

1997 The Coventry Award. The value of preoperative aspiration before total knee revision

Not best available

evidence

Chimento, et al.

1996 Gram stain detection of infection during revision arthroplasty

Not best available

evidence

Della Valle, et al.

1999 The role of intraoperative Gram stain in revision total joint arthroplasty

>10% prostheses

already removed

Ghanem, et al.

2009 Periprosthetic infection: where do we stand with regard to Gram stain?

Not best available

evidence

Ko, et al.

2005

The role of intraoperative frozen section in decision making in revision hip and knee

arthroplasties in a local community hospital

Not best available

evidence

Kraemer, et al.

1993

Bone scan, gallium scan, and hip aspiration in the diagnosis of infected total hip

arthroplasty

Not best available

evidence

Spangehl, et al.

1999


infection at the sites of two hundred and two revision total hip arthroplasties

Not best available

evidence


159

STUDY QUALITY

Table 65. Gram Stain - Quality

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Spangehl 202 Gram stain I ? ● ● ● ● ● ● ● ● ● ? ● ● ●

Banit 63 Gram stain I ● ● ● ● ● ● ● ● ● ? ● ● ● ●

Banit 55 Gram stain I ● ● ● ● ● ● ● ● ● ? ● ● ● ●

Parvizi 70 Gram stain -

tissue II ● ● ● ● ● ● ● ○ ○ ? ? ● ● ●

Parvizi 70 Gram stain -

fluid II ● ● ● ● ● ● ● ○ ○ ? ? ● ● ●


160

STUDY RESULTS

Figure 21. Gram Stain Results - Likelihood Ratios

StudyId

Parvizi - fluid

Parvizi - tissue

Banit

Spangehl

1 2 5 10

DLR POSITIVE

StudyId

Parvizi - fluid

Parvizi - tissue

Banit

Spangehl

1.1 .2 .5

DLR NEGATIVE


161

Table 66. Intraoperative Gram Stain Results

Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Spangehl 202 Gram

stain

At least 1 of: 1)open

wound or sinus

communicating with

the joint 2)purulent


3)positive

investigations in a

minumum of 3 of the

following: ESR >30

mm/h, CRP

>10mg/L,

preoperative

aspiration ≥1 positive

culture, frozen

section >5 PMNs/hpf,


>1/3 positive cultures

Hip 10.8

(2.74, 42.6)

0.83

(0.69, 0.99)

0.19

(0.06,

0.38)

0.98

(0.95, 1) 5 3 22 172

I Banit 63 Gram

stain

Intraoperative

cultures Hip

39.75

(2.29,

689.8)

0.63

(0.41, 0.98)

0.36

(0.11,

0.69)

1

(0.93, 1) 4 0 7 52

I Banit 55 Gram

stain

Intraoperative

cultures Knee

42.3

(2.47,

724.7)

0.56

(0.32, 0.97)

0.44

(0.14,

0.79)

1

(0.92, 1) 4 0 5 46


162

Table 66. Intraoperative Gram Stain Results (Continued)

Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio (95%

CI)

Sensitivity

(95% CI)

Specificity


II Parvizi 70

Gram

stain -

tissue

at least 3 of: 1)CRP

>1mg/dL 2)ESR

>30mm/hr 3)positive

joint aspiration

culture 4)purulent

intraoperative tissue

appearance 5)positive


Knee

13.6

(0.82,

226.8)

0.8

(0.68, 0.95)

0.21

(0.09, 0.36)

1

(0.89, 1) 8 0 31 31

II Parvizi 70

Gram

stain -

fluid

at least 3 of: 1)CRP

>1mg/dL 2)ESR

>30mm/hr 3)positive

joint aspiration

culture 4)purulent




Knee 11.13

(1.55, 80.1)

0.66

(0.52, 0.85)

0.36

(0.21, 0.53)

0.97

(0.83, 1) 14 1 25 30


163

RECOMMENDATION 12 We recommend the use of frozen sections of peri-implant tissues in patients who are

undergoing reoperation for whom the diagnosis of periprosthetic joint infection has not

been established or excluded.









Rationale

Eight Level I studies were identified that evaluated the use of frozen sections to help

diagnose peri-implant infection.3, 21, 30, 32, 54, 59, 75, 96

Three studies excluded patients with

known underlying inflammatory arthropathy.30, 54, 96

Six of the eight studies used intraoperative cultures, while two studies used a combination

of test results as the gold standard for diagnosis against which the frozen sections were

compared. All studies based the histologic diagnosis of probable infection on the tissue

concentration of acute inflammatory cells, usually defined by two variables: 1) the

number of neutrophils in a high magnification (400X) microscopic field, and 2) the

minimum number of fields containing that concentration of neutrophils. At least three

studies excluded neutrophils entrapped in superficial fibrin.

Four studies used 10 or more neutrophils per high power field, and three of the four

required 10 more neutrophils in at least 5 fields. The remaining study required 10 or more

neutrophils in any given area. Our meta-analysis of these studies indicated that frozen

section is a very good “rule in” test (i.e., a positive result has a high likelihood of

infection; LR+: 23), but is a relatively low value “rule out” test (i.e. a negative result does

not have a high likelihood of absent infection; LR-: 0.23).

Four other studies used 5 or more neutrophils per high power field; several of these

specified at least 5 microscopic fields but the other studies did not. Meta-analysis

indicated that when compared to a 10 PMN/HPF criterion this lower inflammation

threshold may have similar sensitivity, but slightly lower specificity (i.e. a higher

frequency of false positive results).

There is insufficient information to distinguish 5 from 10 neutrophils per high power

field as the best threshold needed for diagnosis. Insufficient information is available to


164

determine the efficacy of frozen sections in patients with an underlying inflammatory

arthropathy.


165

Supporting Evidence

We included eight studies with reliable data (two hip, one knee, two each, three mixed)

that addressed the diagnostic utility of frozen sections.3, 21, 30, 32, 54, 59, 75, 96

Meta-analysis

of these studies indicated between-study heterogeneity (I2=64%), possibly due to one

study which did not have a quantitative definition of infection seen on frozen section.30

Four studies used 10 or more neutrophils in five fields as a threshold. Meta-analysis of

these latter studies indicated that frozen section using this threshold was a very good

“rule in” test (positive LR = 23.4) and not as good as a “rule out” test (negative LR =

0.23). Four studies used a threshold of 5 PMN/HPF; meta-analysis of these studies

indicated a moderately good “rule in” test and not as good of a “rule out” test (positive

LR = 9.1, negative LR = 0.22). Five studies reported sampling suspicious-appearing sites,

and three reported excluding the histology of fibrin.

SUMMARY OF EVIDENCE

Table 67. Frozen Section Summary of Evidence

Test

Number

of

Studies

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity

(95% CI)

Frozen section -

threshold of 10

PMN in 5 HPF

(I2=0%)

4 23.4

(11.7, 47.1)

0.23

(0.14, 0.36)

0.78

(0.66, 0.86)

0.97

(0.94, 0.98)

Frozen section -

threshold of 5

PMN/HPF

(I2=0%)

4 9.1

(4.8, 17.2)

0.22

(0.13, 0.36)

0.80

(0.68, 0.88)

0.91

(0.84, 0.95)


166

EXCLUDED ARTICLES



Abdul-Karim, et al.

1998

Frozen section biopsy assessment for the presence of polymorphonuclear leukocytes in

patients undergoing revision of arthroplasties

Not best available

evidence

Athanasou, et al.

1995 Diagnosis of infection by frozen section during revision arthroplasty

Not best available

evidence

Bori, et al.

2006

Low sensitivity of histology to predict the presence of microorganisms in suspected aseptic

loosening of a joint prosthesis

Not best available

evidence

Charosky, et al.

1973 Total hip replacement failures. A histological evaluation <25 patients

Della Valle, et al.

1999

Analysis of frozen sections of intraoperative specimens obtained at the time of reoperation

after hip or knee resection arthroplasty for the treatment of infection

>10% prostheses

already removed

Fehring, et al.


Not best available

evidence

Feldman, et al.


Not best available

evidence

Kanner, et al.

2008 Reassessment of the usefulness of frozen section analysis for hip and knee joint revisions

Not best available

evidence

Kataoka, et al.

2002

An assessment of histopathological criteria for infection in joint arthroplasty in rheumatoid

synovium

Not relevant - not

specific to revision

surgery

Mirra, et al.

1976 The pathology of the joint tissues and its clinical relevance in prosthesis failure

Not best available

evidence

Mirra, et al.

1982 The pathology of failed total joint arthroplasty

Not best available

evidence


167



Musso, et al.

2003 Role of frozen section histology in diagnosis of infection during revision arthroplasty

>10% prostheses

already removed

Pons, et al.

1999 Infected total hip arthroplasty--the value of intraoperative histology

Not best available

evidence

Rosas, et al.

1998


joint replacement infection

<25

patients/insufficient

data

Spangehl, et al.

1999


infection at the sites of two hundred and two revision total hip arthroplasties

Not best available

evidence

Wong, et al.

2005

Intraoperative frozen section for detecting active infection in failed hip and knee

arthroplasties

Not best available

evidence


168

STUDY QUALITY

Table 69. Frozen Section - Quality

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Banit 63 Frozen section: >10 PMNs/high power

field in any of the sampled areas I ● ● ● ● ● ● ● ● ● ● ● ● ● ●





Della

Valle 94

Frozen section: avg. of >10 PMN seen

within tissue (not fibrin) in the 5 most

cellular fields seen

I ● ● ● ● ● ● ● ● ● ● ? ? ● ●

Fehring 97

Frozen section: acute inflammation

characterized by the presence of PMNs

(specific criteria of number per field

not established)

I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Frances

Borrego 83

Frozen section: >10 PMNs/hpf in 5

fields I ● ● ● ● ● ● ● ● ● ● ● ● ● ●


169

Table 69. Frozen Section – Quality (Continued)

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dard

ex

ecu

tio

n

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Frances

Borrego 63

Frozen section: >10 PMNs/hpf in 5

fields I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Ko 40 Frozen section: >5 PMNs/HPF I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Lonner 175 Frozen section: ≥10PMNs/hpf in 5

fields I ● ● ● ● ● ● ● ● ● ● ● ? ● ●

Lonner 175 Frozen section: ≥5 PMNs/hpf in 5

fields I ● ● ● ● ● ● ● ● ● ● ● ? ● ●

Nunez 136 Frozen section: ≥5 PMNs/hpf

(looked at 10 fields) I ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Schinsky 201 Frozen section: avg. of >10PMN

in the 5 most cellular HPF I ● ● ● ● ● ● ● ● ● ? ? ● ● ●


170

STUDY RESULTS

Figure 22. Frozen Section Meta-Analysis – Threshold of 10 PMN in 5 Fields

StudyId

COMBINED

Schinsky

Della Valle

Lonner

Frances Borrego

1 2 5 10

DLR POSITIVE

StudyId

COMBINED

Schinsky

Della Valle

Lonner

Frances Borrego

1.1 .2 .5

DLR NEGATIVE

Figure 23. Frozen Section Meta-Analysis – Threshold of 5 PMN/HPF

StudyId

COMBINED

Nunez

Ko

Lonner

Banit

1 2 5 10

DLR POSITIVE

StudyId

COMBINED

Nunez

Ko

Lonner

Banit

1.1 .2 .5

DLR NEGATIVE


171

Figure 24. Frozen Section Results - Likelihood Ratios – Mixed Thresholds

StudyId

Fehring

Ko

Nunez

Banit

Frances Borrego

Schinsky

Della Valle

Lonner

1 2 5 10

DLR POSITIVE

StudyId

Fehring

Ko

Nunez

Banit

Frances Borrego

Schinsky

Della Valle

Lonner

1.1 .2 .5

DLR NEGATIVE


172

Table 70. Frozen Section Results

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Banit 63

Frozen

Section

(>10

PMNs/HPF

in any of the

sampled

areas)

Intraoperative

Cultures Hip

5.91

(1.88,

18.52)

0.59

(0.34, 1.02)

0.45

(0.17,

0.77)

0.92

(0.81,

0.98)

5 4 6 48

I Frances

Borrego 83

Frozen

Section

(>10

PMNs/HPF

in 5 fields)

Intraoperative

Cultures Hip

76

(4.45,

1299.33)

0.5

(0.26, 0.97)

0.5

(0.16,

0.84)

1

(0.95, 1) 4 0 4 75

I Schinsky 201

Frozen

Section

(avg. of >10

PMNs in the

5 most

cellular

HPF)

At least 2 of: 1)a

positive

intraoperative

culture (on solid

media) 2)gross

purulence 3)final

histopathology

(avg. of >10

PMNs in the 5

most cellular

HPF)

Hip

11.8

(6.14,

22.67)

0.29

(0.19, 0.45)

0.73

(0.59,

0.84)

0.94

(0.89,

0.97)

40 9 15 137


173

Table 70. Frozen Section Results (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Nunez 136

Frozen

Section (≥5

PMN/HPF;

looked at 10

fields)

Intraoperative

Cultures Hip

6.78

(3.86,

11.92)

0.16

(0.08,

0.33)

0.86

(0.73,

0.94)

0.87

(0.79,

0.94)

42 11 7° 76

I Banit 55

Frozen

Section

(>10

PMNs/HPF

in any of the

sampled

areas)

Intraoperative

Cultures Knee

17.86

(5.3,

60.16)

0.05

(0, 0.79)

1

(0.66, 1)

0.96

(0.85,

0.99)

9 2 0 44


174


Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Della

Valle 94

Frozen

Section

(avg. of >10

PMNs in the

5 most

cellular

HPF)

At least 2 of 3

positive

intraoperative

cultures on

solid media or

2 of following:

1)one positive

culture 2)final

histopathology

consistent with

infection

3)gross

purulence seen

at time of

revision

Knee

23.27

(5.95,

91.05)

0.13

(0.06,

0.29)

0.88

(0.74,

0.96)

0.96

(0.87, 1) 36 2 5 51

I Frances

Borrego 63

Frozen

Section

(>10

PMNs/hpf

in 5 fields)

Intraoperative

Cultures Knee

6.5

(2.46,

17.16)

0.37

(0.21,

0.66)

0.67

(0.45,

0.84)

0.90

(0.76,

0.97)

16 4 8 35

I Banit 63

Frozen

Section (>5

PMNs/HPF

in any of the

sampled

areas)

Intraoperative

Cultures

Mixed

(63 hip,

55 knee,

3

shoulder)

4.17

(2.42,

7.16)

0.40

(0.22,

0.73)

0.67

(0.43,

0.85)

0.84

(0.75,

0.910

14 16 7 84


175


Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Fehring 97

Frozen

Section

(Presence of

PMNs (no

specific

criteria of

number per

field)

Intraoperative

Cultures Mixed

1.74

(0.43,

7.03)

0.91

(0.69,

1.22)

0.18

(0.02,

0.52)

0.90

(0.81,

0.95)

2 9* 9 77

I Ko 40

Frozen

Section (>5

PMNs/HPF)

Intraoperative

Cultures

Mixed

(34 hip,

6 knee)

20.67

(2.85,

150.1)

0.34

(0.14,

0.87)

0.67

(0.3, 0.93)

0.97

(0.83, 1) 6 1 3 30

I Lonner 175

Frozen

Section

(≥10

PMN/HPF

in 5 fields)

Intraoperative

Cultures

Mixed

(142 hip,

33 knee)

65.7

(16.4, 264)

0.16

(0.06,

0.45)

0.84

(0.60,

0.97)

0.99

(0.95, 1) 16 2 3 154

I Lonner 175

Frozen

Section (≥5

PMN/HPF

in 5 fields)

Intraoperative

Cultures

Mixed

(142 hip,

33 knee)

18.8

(8.87,

39.7)

0.17

(0.06,

0.47)

0.84

(0.60,

0.97)

0.96

(0.91,

0.98)

16 7 3 149

°Three of seven positive cultures considered possible contaminants due to negative clinical and intraoperative findings

*Study noted 6 cases with negative cultures but high clinical suspicion of infection; 3 cases with indeterminate results not included


176

RECOMMENDATION 13 We recommend that multiple cultures be obtained at the time of reoperation in patients

being assessed for periprosthetic joint infection.









Rationale

Four Level I studies compared the effects of using one as opposed to more than one

positive culture as a threshold for diagnosing infection, with histology of peri-implant

tissue as the gold standard.2, 94, 104, 105

Two of these studies obtained at least three cultures

per patient and two of these studies obtained at least two cultures per patient. Compared

to histology, more than one positive culture result had a higher positive likelihood ratio

for diagnosing infection than a single positive culture result.

Assessing infection using multiple cultures increases the chances of identifying infection.

Cultures are easily performed during the procedure and provide reliable results as

indicated by the postive likelihood ratio. Obtaining more than one culture decreases the

likelihood of false negative result and may assist the clinician in clarifying a result that

may be deemed a false positive based on the results of other tests.

Supporting Evidence

Four studies presented reliable data on the effects of using one or more than one positive

culture as a threshold for infection.2, 94, 104, 105

In these studies, authors sampled from the

“most suspicious areas” or “areas that appear to be most infected or inflamed”. In these

studies, cultures were compared to histologic findings or a combination of histologic

findings, visible purulence, and a sinus tract communicating with the prosthesis. There

was between-study heterogeneity in each category. Samples were taken for aerobic and

anaerobic culture in each study.

One study with moderately reliable data compared swab vs. tissue,99

and another study

with less reliable data compared fluid vs. tissue.78

In each study, the differences between

the two techniques were not statistically significant.


177

SUMMARY OF EVIDENCE

Table 71. Summary of Evidence

Test

Number

of

Studies

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity

(95% CI)

Intraoperative

Cultures (≥1

positive culture) –

range

4 2.87 – 8.1 0.09 – 0.29 0.73 – 0.94 0.67 – 0.91

Intraoperative

Cultures (≥2

positive cultures)

– range

4 11.5 – 76.6 0.25 – 0.47 0.54 – 0.77 0.93 – 0.99

*Range presented because meta-analysis indicated heterogeneity


178

EXCLUDED ARTICLES



Baker, et al.

1994

Use of Sentinel blood culture system for analysis of specimens from potentially infected

prosthetic joints

Does not address

recommendation

Bare, et al.

2006 Preoperative evaluations in revision total knee arthroplasty

Not best available

evidence

Barrack, et al.

2007

The fate of the unexpected positive intraoperative cultures after revision total knee

arthroplasty

Not best available

evidence

Barrack, et al.

1993 The value of aspiration of the hip joint before revision total hip arthroplasty

Not best available

evidence

Berend, et al.

2007

Unexpected positive intraoperative cultures and gram stain in revision total hip

arthroplasty for presumed aseptic failure

Not best available

evidence

Cune, et al.

2008

A Superficial Swab Culture is Useful for Microbiologic Diagnosis in Acute Prosthetic

Joint Infections

Not best available

evidence

Duff, et al.


Not best available

evidence

Dupont,

1986 Significance of operative cultures in total hip arthroplasty Insufficient Data

Fehring, et al.


Not best available

evidence

Feldman, et al.


Not best available

evidence

Fitzgerald, et al.

1973 Bacterial colonization of wounds and sepsis in total hip arthroplasty

Does not address

recommendation

Ince, et al.

2004

Is 'aseptic' loosening of the prosthetic cup after total hip replacement due to nonculturable

bacterial pathogens in patients with low-grade infection? <25 patients


179



Levine, et al.

2001 Use of blood culture vial specimens in intraoperative detection of infection <25 patients

Marculescu, et al.

2005 Prosthetic joint infection diagnosed postoperatively by intraoperative culture

Does not address

recommendation

Mehra, et al.

2006 Bacteriology swab in primary total hip arthroplasty-- does it have a role?

Does not address

recommendation

Mikkelsen, et al.

2006 Culture of multiple peroperative biopsies and diagnosis of infected knee arthroplasties

Not best available

evidence

Moojen, et al.

2007

Identification of orthopaedic infections using broad-range polymerase chain reaction and

reverse line blot hybridization

Not best available

evidence

Muller, et al.

2008




Not best available

evidence

Neut, et al.

2003 Detection of biomaterial-associated infections in orthopaedic joint implants <25 patients

Padgett, et al.

1995 Efficacy of intraoperative cultures obtained during revision total hip arthroplasty

Not best available

evidence

Pandey, et al.

2000

Histological and microbiological findings in non-infected and infected revision

arthroplasty tissues. The OSIRIS Collaborative Study Group. Oxford Skeletal Infection

Research and Intervention Service

Not best available

evidence

Panousis, et al.

2005

Poor predictive value of broad-range PCR for the detection of arthroplasty infection in 92

cases

Not best available

evidence

Picado, et al.

2008 Accuracy of intraoperative cultures in primary total hip arthroplasty

Does not address

recommendation

Pipino, et al.

1989 Bacteriological and histological study of 40 loose cemented hip prostheses Insufficient Data


180



Pizzoferrato, et al.

1980 Microbiological investigation of 161 cases of hip endo-arthroprosthesis failure Insufficient Data

Ringberg, et al.

1998

Bacteriologic evidence of infection caused by coagulase-negative staphylococci in total hip

replacement

Does not address

recommendation

Schinsky, et al.

2008

Perioperative testing for joint infection in patients undergoing revision total hip

arthroplasty

Not best available

evidence

Spangehl, et al.

1999


arthroplasty

Not best available

evidence

Tietjen, et al.

1977 The significance of intracapsular cultures in total hip operations

Not best available

evidence


181

STUDY QUALITY

Table 73. Intraoperative Cultures - Quality

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Atkins 297 Intraoperative Cultures (≥3) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Atkins 213 Intraoperative Cultures (≥3) I ? ● ● ● ● ● ● ● ● ● ? ● ● ●


Atkins 297 Intraoperative Cultures (≥1, solid or

broth) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●


broth) I ? ● ● ● ● ● ● ● ● ● ? ● ● ●


broth) I ? ● ● ● ● ● ● ● ● ● ? ● ● ●

Atkins 297 Intraoperative Cultures (≥2) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●



Schafer 284 Intraoperative Cultures (≥1) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Schafer 284 Intraoperative Cultures (≥2) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●


182

Table 73. Intraoperative Cultures – Quality (Continued)

● = Yes

○ = No

? = Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Trampuz

2006 78 Intraoperative Cultures (≥1) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●

Trampuz


Trampuz


Trampuz


Spangehl 180 Intraoperative culture of tissue

(>1/3 of sample positive) III ● ● ● ● ● ● ○ ● ● ● ? ● ● ●

Spangehl 168 Intraoperative swab culture (>1/3

of samples positive) III ● ● ● ● ● ● ○ ● ● ● ? ● ● ●

Parvizi 70 Intraoperative fluid culture IV ● ● ● ● ● ● ○ ○ ○ ● ? ● ● ●

Parvizi 70 Intraoperative tissue culture IV ● ● ● ● ● ● ○ ○ ○ ● ? ● ● ●


183

STUDY RESULTS

Figure 25. Intraoperative Cultures Results - Threshold of 1 vs. 2 Positive Cultures

StudyId

Trampuz (2007) - 2

Atkins - 2

Trampuz (2006) - 2

Schafer - 2

Trampuz (2007) - 1

Atkins - 1

Trampuz (2006) - 1

Schafer - 1

1 2 5 10

DLR POSITIVE

StudyId

Trampuz (2007) - 2

Atkins - 2

Trampuz (2006) - 2

Schafer - 2

Trampuz (2007) - 1

Atkins - 1

Trampuz (2006) - 1

Schafer - 1

1.1 .2 .5

DLR NEGATIVE

Figure 26. Intraoperative Cultures Results - Tissue or Swab or Fluid

StudyId

Parvizi - fluid

Parvizi - tissue

Spangehl - tissue

Spangehl - swab

1 2 5 10

DLR POSITIVE

StudyId

Parvizi - fluid

Parvizi - tissue

Spangehl - tissue

Spangehl - swab

1.1 .2 .5

DLR NEGATIVE


184

Table 74. Overall and number of cultures results

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Schafer 284 Intraoperative

Cultures (≥1) Histology

Mixed

(145

hip,

139

knee)

2.87

(2.32,

3.56)

0.09

(0.04,

0.19)

0.94

(0.88,

0.98)

0.67

(0.6, 0.74) 98 59 6 121

I Trampuz

2006 78

Intraoperative

Cultures (≥1)

At least 1 of:

1)visible

purulence of

synovial fluid

or area

surrounding the

prosthesis

2)acute

inflammation

on

histopathologic

exam of

permanent

periprosthetic

tissue sections

3)a sinus tract

communicating

with the

prosthesis

Mixed

(68

knee,

10

hip)

8.1

(3.41,

19.26)

0.28

(0.14,

0.55)

0.75

(0.53, 0.9)

0.91

(0.8, 0.97) 18 5 6 49


185

Table 74. Overall and number of cultures results (Continued)

Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Atkins

(all) 297

Intraoperative


Mixed

(253

hip,

44

knee)

4.33

(3.25,

5.78)

0.21

(0.11,

0.42)

0.83

(0.68,

0.93)

0.81

(0.75,

0.85)

34 49 7 207

I

Atkins

(patients

with 3-6

samples)

213 Intraoperative


Mixed

(253

hip,

44

knee)

4.01

(2.89,

5.56)

0.22

(0.1, 0.48)

0.83

(0.64,

0.94)

0.79

(0.73,

0.85)

24 38 5 146

I

Atkins

(patients

operated

on by

most

consistent

sureons)

239 Intraoperative


Mixed

(253

hip,

44

knee)

4.37

(3.19,

5.98)

0.19

(0.08,

0.42)

0.85

(0.68,

0.95)

0.81

(0.75,

0.86)

28 40 5 166


186


Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Trampuz

2007 331

Intraoperative

Cultures (≥1)

At least 1 of:

1)visible

purulence of

synovial fluid

or area

surrounding

the prosthesis

2)acute

inflammation

on

histopathologic

exam of

permanent

periprosthetic

tissue sections

3)a sinus tract

communicating

with the

prosthesis

Mixed

(207

knee,

124

hip)

8.04

(5.33,

12.14)

0.29

(0.2, 0.42)

0.73

(0.62,

0.83)

0.91

(0.87,

0.94)

58 23 21 229

I Schafer 284 Intraoperative


Mixed

(145

hip,

139

knee)

11.54

(6.61,

20.13)

0.25

(0.17,

0.35)

0.77

(0.68,

0.85)

0.93

(0.89,

0.97)

80 12 24 168


187


Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Trampuz

2006 78

Intraoperative

Cultures (≥2)

At least 1 of:

1)visible

purulence of

synovial fluid

or area

surrounding

the prosthesis

2)acute

inflammation

on

histopathologic

exam of

permanent

periprosthetic

tissue sections

3)a sinus tract

communicating

with the

prosthesis

Mixed

(68

knee,

10

hip)

29.25

(4.05, 211)

0.47

(0.3, 0.72)

0.54

(0.33,

0.74)

0.98

(0.9, 1) 13 1 11 53

I Atkins

(all) 297

Intraoperative


Mixed

(253

hip,

44

knee)

25.87

(12.1,

55.1)

0.3

(0.19,

0.48)

0.71

(0.54,

0.84)

0.97

(0.94,

0.99)

29 7 12 249


188


Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I

Atkins

(patients

with 3-6

samples)

213 Intraoperative


Mixed

(253

hip,

44

knee)

24.11

(9.76,

59.54)

0.35

(0.21,

0.59)

0.66

(0.46,

0.82)

0.97

(0.94,

0.99)

19 5 10 179

I

Atkins

(patients

operated

on by

most

consistent

sureons)

239 Intraoperative


Mixed

(253

hip,

44

knee)

25.0

(11.1,

56.5)

0.28

(0.16,

0.49)

0.73

(0.54,

0.87)

0.97

(0.94,

0.99)

24 6 9 200


189


Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I Trampuz

2007 331

Intraoperative

Cultures (≥2)

At least 1 of:

1)visible

purulence of

synovial fluid

or area

surrounding

the prosthesis

2)acute

inflammation

on

histopathologic

exam of

permanent

periprosthetic

tissue sections

3)a sinus tract

communicating

with the

prosthesis

Mixed

(207

knee,

124

hip)

76.6

(19.0, 308)

0.4

(0.3, 0.52)

0.61

(0.49,

0.72)

0.99

(0.97, 1) 48 2 31 250

I Atkins

(all) 297

Intraoperative


Mixed

(253

hip,

44

knee)

168

(23.6,

1207)

0.34

(0.22,

0.52)

0.66

(0.49, 0.8)

1

(0.98, 1) 27 1 142 255


190


Level of


Reference

Standard Joint

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


I

Atkins

(patients

with 3-6

samples)

213 Intraoperative


Mixed

(253

hip,

44

knee)

114

(15.8, 823)

0.38

(0.24,

0.61)

0.62

(0.42,

0.79)

0.99

(0.97, 1) 18 1 11 183

I

Atkins

(patients

operated

on by

most

consistent

sureons)

239 Intraoperative


Mixed

(253

hip,

44

knee)

144

(20.1,

1028)

0.3

(0.18,

0.51)

0.7

(0.51,

0.84)

1

(0.97, 1) 23 1 10 205


191

Table 75. Tissue vs. Swab vs. Fluid

Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


III Spangehl 168

Intraoperative

Swab

Cultures

(>1/3 of

samples

positive)


wound of sinus in

communication with






least 3



aspiration with at least

1 positive culture,

frozen section with

>5PMN/HPF,


(>1/3 of cultures

positive)

Hip 115

(16.1, 829)

0.24

(0.1, 0.56)

0.76

(0.5, 0.93)

0.99

(0.96, 1) 13 1 4 150


192

Table 75. Tissue vs. Swab vs. Fluid (Continued)

Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


III Spangehl 180

Intraoperative

Tissue

Cultures

(>1/3 of

sample

positive)


wound of sinus in

communication with






least 3



aspiration with at least

1 positive culture,

frozen section with

>5PMN/HPF,


(>1/3 of cultures

positive)

Hip

30.6

(12.8,

73.1)

0.06

(0.01,

0.39)

0.94

(0.73, 1)

0.97

(0.93,

0.99)

17 5 1 157


193

Table 75. Tissue vs. Swab vs. Fluid (Continued)

Level of


Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Sensitivity

(95% CI)

Specificity


IV Parvizi 70

Intraoperative

Tissue

Culture

At least 3 of: 1)CRP

>1mg/dL 2)ESR

>30mm/hr 3)positive

joint aspiration culture

4)purulent




Knee 53.6

(3.41, 841)

0.17

(0.08,

0.33)

0.85

(0.69,

0.94)

1

(0.89, 1) 33 0 6 31

IV Parvizi 70 Intraoperative

Fluid Culture

At least 3 of: 1)CRP

>1mg/dL 2)ESR

>30mm/hr 3)positive

joint aspiration culture

4)purulent




Knee 27.8

(4.03, 191)

0.11

(0.04,

0.27)

0.9

(0.76,

0.97)

0.97

(0.83, 1) 35 1 4 30


194

RECOMMENDATION 14 We recommend against initiating antibiotic treatment in patients with suspected

periprosthetic joint infection until after cultures from the joint have been obtained.









Rationale

One Level I study addressed whether administration of antibiotic therapy prior to

obtaining cultures from the joint affected the sensitivity of the cultures in diagnosing

periprosthetic infections.105

The study found a false negative rate of 55% in patients

receiving antibiotics within the previous 14 days compared to 23% in patients not

receiving antibiotics during the same time period. The difference was statistically

significant. Hence, there is a concern that antibiotics can interfere with isolation of the

infecting organism leading to confusion regarding the diagnosis or inability to use

organism specific antibiotics subsequently when infection is confirmed. Thus,

administration of oral or intravenous antibiotics to patients with suspected diagnosis of

periprosthetic joint infection is discouraged, until aspiration of the joint is performed or

samples for culture are obtained.

The finding of only one Level I study supporting this recommendation would be

evaluated as moderate strength. However, because of the severity of the potential harm to

the patient in getting a false negative culture result, the strength of the recommendation

was elevated to strong.

Supporting Evidence

One included study with reliable data addressed whether antibiotic therapy decreases the

sensitivity of intraoperative cultures in diagnosing periprosthetic infection.105

The group

of patients who had received antimicrobial therapy within 14 days of surgery had a

statistically significantly higher rate of false-negative culture results than those who had

not. In this study, a positive result was defined as growth from at least two specimens.


195

EXCLUDED ARTICLES

Table 76. Excluded Articles - Recommendation14


Barrack, et al.

1997 The Coventry Award. The value of preoperative aspiration before total knee revision <25 patients/arm

Datz, et al.


Not relevant - not

specific to pji

Spangehl, et al.

1999


infection at the sites of two hundred and two revision total hip arthroplasties <25 patients/arm

Spangehl, et al.

1999



Trampuz, et al.

2006


infection is associated with risk of contamination <25 patients


196

STUDY QUALITY

Table 77. Preoperative Antibiotic Therapy - Quality

● = Yes

○ = No

? =Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Trampuz 78 Intraoperative

Cultures (≥2) I ● ● ● ● ● ● ● ● ● ● ? ● ● ●


197

STUDY RESULTS


Level of

Evidence Author N Joint Reference Standard False Negatives Risk Ratio

p-

value

I Trampuz 79 Mixed

At least 1 of: 1)visible purulence of synovial

fluid or area surrounding the prosthesis

2)acute inflammation on histopathologic

exam of permanent periprosthetic tissue

sections 3)a sinus tract communicating with

the prosthesis

Antibiotics within 14 days: 55%

No antibiotics within 14 days: 23%

2.38

(1.26,

4.51)

0.004


198

RECOMMENDATION 15 We suggest that prophylactic pre-operative antibiotics not be withheld in patients at lower

probability for periprosthetic infection and those with an established diagnosis of

periprosthetic joint infection who are undergoing reoperation.









Rationale

Two Level II studies and two joint registry studies found that the administration of

perioperative antibiotics significantly decreased the risk of postoperative infection.14, 26,

28, 43

These studies however, do not address whether or not the administration of

preoperative antibiotics interfere with intraoperative cultures. One Level III study did not

find a significant difference in the false negative rate of intraoperative knee cultures in

patients receiving perioperative antibiotic prophylaxis (12.5 vs. 8.1%; p=0.34).34

Patients who contract periprosthetic infection face catastrophic complications including

additional surgery, increased cost and prolonged treatment, as well as possible permanent

loss of the prosthesis. The important role of antibiotic prophylaxis in helping to prevent

these catastrophic events outweighs the potential risks.

Supporting Evidence

Two RCTs, neither specific to patients undergoing revision, compared preoperative

antibiotics to placebo.14, 26

Two joint registry studies, one of which was specific to

patients undergoing revision, compared antibiotic prophylaxis (systemic and/or cement)

to no antibiotic prophylaxis.28, 43

The two RCTs and one of the joint registry studies were

of hip patients; the other joint registry study was of knee patients. The studies’ results

indicated a higher risk of infection when antibiotics were not used. The results are

presented in Table 84 and Table 85.

One included study with moderately reliable data addressed whether administration of

preoperative antibiotics decreases the sensitivity of intraoperative cultures in diagnosing

periprosthetic infection.34

Among patients in whom the infecting organism had been

isolated from the preoperative aspiration, the rate of false-negative intraoperative culture

results was not statistically significantly different between the group of patients who had

received antibiotics and the group who had not.


199

EXCLUDED ARTICLES



Akre, et al.

2000 Risk for gastric cancer after antibiotic prophylaxis in patients undergoing hip replacement

Does not address

recommendation

AlBuhairan, et al.

2008 Antibiotic prophylaxis for wound infections in total joint arthroplasty: a systematic review

Systematic review,


Bratzler, et al.

2004

Antimicrobial prophylaxis for surgery: An advisory statement from the national surgical

infection prevention project

Narrative review,


Chodak, et al.

1977 Use of systemic antibiotics for prophylaxis in surgery: a critical review

Systematic review,


de Lalla, et al.

1993

Regional and systemic prophylaxis with teicoplanin in monolateral and bilateral total knee

replacement procedures: study of pharmacokinetics and tissue penetration

Not best available

evidence

Ericson, et al.

1973 Cloxacillin in the prophylaxis of postoperative infections of the hip Duplicate data

Eshkenazi, et al.

2001

Serum and synovial vancomycin concentrations following prophylactic administration in

knee arthroplasty

Not best available

evidence

Espehaug, et al.

1997 Antibiotic prophylaxis in total hip arthroplasty Duplicate data

Gillespie, et al.

2001

Antibiotic prophylaxis for surgery for proximal femoral and other closed long bone

fractures

Does not address

recommendation

Glenny, et al.

1999 Antimicrobial prophylaxis in total hip replacement: a systematic review

Systematic review,


Hill, et al.

1981

Prophylactic cefazolin versus placebo in total hip replacement. Report of a multicentre

double-blind randomised trial Duplicate data

Hughes, et al.

1979

Treatment of subacute sepsis of the hip by antibiotics and joint replacement. Criteria for

diagnosis with evaluation of twenty-six cases

Does not address

recommendation


200



Isacson, et al.

1984

Renal impairment after high doses of dicloxacillin-prophylaxis in joint replacement

surgery

Does not address

recommendation

Johnson,

1987 Antibiotic prophylaxis with cefuroxime in arthroplasty of the knee <25 patients

Klenerman, et al.

1991

Combined prophylactic effect of ultraclean air and cefuroxime for reducing infection in

prosthetic surgery

Not best available

evidence

Lidwell, et al.

1987

Ultraclean air and antibiotics for prevention of postoperative infection. A multicenter study

of 8,052 joint replacement operations Duplicate data

Lidwell, et al.

1984

Infection and sepsis after operations for total hip or knee-joint replacement: influence of

ultraclean air, prophylactic antibiotics and other factors Duplicate data

Lidwell, et al.

1982

Effect of ultraclean air in operating rooms on deep sepsis in the joint after total hip or knee

replacement: a randomised study

Not best available

evidence

Mannien, et al.

2006 Effect of optimized antibiotic prophylaxis on the incidence of surgical site infection

Not best available

evidence

Marotte, et al.

1987

Infection rate in total hip arthroplasty as a function of air cleanliness and antibiotic

prophylaxis. 10-year experience with 2,384 cementless Lord madreporic prostheses

Not best available

evidence

McQueen, et al.

1987

A comparison of systemic cefuroxime and cefuroxime loaded bone cement in the

prevention of early infection after total joint replacement

Does not address

recommendation

Mini, et al.

2001

Preliminary results of a survey of the use of antimicrobial agents as prophylaxis in

orthopedic surgery

Does not address

recommendation

Nelson, et al.

1993

A comparison of gentamicin-impregnated polymethylmethacrylate bead implantation to

conventional parenteral antibiotic therapy in infected total hip and knee arthroplasty

Does not address

recommendation

Nelson, et al.

1980

The effect of previous surgery, operating room environment, and preventive antibiotics on

postoperative infection following total hip arthroplasty

Not best available

evidence

Norden,

1983 A critical review of antibiotic prophylaxis in orthopedic surgery

Narrative review,



201



Parvizi, et al.

2008 Diagnosis of infected total knee: findings of a multicenter database Duplicate Data

Schulitz, et al.

1980

The prophylactic use of antibiotics in alloarthroplasty of the hip joint for coxarthrosis. A

randomized study

Antibiotics not given

preoperatively

Van Kasteren, et al.

2007

Antibiotic prophylaxis and the risk of surgical site infections following total hip

arthroplasty: Timely administration is the most important factor

Does not address

recommendation


202

STUDY QUALITY

Table 80. Preoperative Antibiotics - Diagnostic Study Quality

● = Yes

○ = No

? =Unclear

Sp

ectr

um

bia

s av

oid

ed

Sel

ecti

on

cri

teri

a d

escr

ibed

Ap

pro

pri

ate

refe

ren

ce s

tan

dar

d

Dis

ease

pro

gre

ssio

n b

ias

avo

ided

Par

tial

ver

ific

atio

n b

ias

avo

ided

Dif

fere

nti

al v

erif

icat

ion b

ias

avo

ided

Inco

rpo

rati

on b

ias

avo

ided

Ind

ex t

est

exec

uti

on

des

crib

ed

Ref

eren

ce s

tan

dar

d e

xec

uti

on

des

crib

ed

Tes

t re

vie

w b

ias

avo

ided

Dia

gn

ost

ic r

evie

w b

ias

avo

ided

Cli

nic

al r

evie

w b

ias

avo

ided

Un

inte

rpre

tab

le/I

nte

rmed

iate

tes

t

resu

lt(s

) re

po

rted

Wit

hd

raw

als

exp

lain

ed


Evidence

Ghanem 171 Intraoperative

Cultures (≥1) III ? ● ● ● ● ● ○ ● ● ● ○ ● ● ●


203

Table 81. Preoperative Antibiotics - Randomized Trial Quality

● = Yes

○ = No

? = Not Reported

Sto

chas

tic

Ran

dom

izat

ion

All

oca

tio

n C

once

alm

ent

Su

bje

cts

Bli

nd

Ass

esso

r B

lin

d

>8

0%

Fo

llo

w-U

p

Sim

ilar

in

Ou

tcom

e at

Bas

elin

e


Evidence

Carlsson Cloxacillin Placebo 171 II ? ○ ● ? ○ ●

Carlsson Cloxacillin Placebo 118 II ? ○ ● ? ○ ●

Doyon Cefazolin Placebo 2137 II ? ● ● ○ ● ●

Doyon Cefazolin Placebo 1069 II ? ● ● ○ ○ ●

Table 82. Preoperative Antibiotics - Joint Registry Quality

● = Yes

○ = No

? = Not Reported

n/a = not applicable

Man

dat

ory

Dat

a S

ubm

issi

on

Popula

tion

-Bas

ed R

egis

try

Val

idat

ed D

ata

>90%

of

pat

ients

cap

ture

d

Sta

tist

ical

Qual

ity C

ontr

ol

Mea

sure

s

Per

form

ed

Ensu

res

corr

ect

dia

gnosi

s


Evidence

Engesaeter Cephalosporin

or Penicillin

No

antibiotic 22170 II ○ ● ● ● ● ●

Jamsen

Not specified

(most often

cefuroxime)

No

antibiotic 43149 II ● ● ○ ● ? ●


204

STUDY RESULTS


Level of

Evidence Author N Joint Reference Standard False Negatives

Risk

Ratio

p-

value

III Ghanem 171 Knee

Aspiration culture on

solid media, or on

liquid media if


positive, if CRP,

ESR, and aspirate

leukocyte cell count

and/or neutrophil

percentage were

elevated in presence

of intraoperative

purulent material

Antibiotics:

12.5%

No antibiotics:

8.1%

1.55

(0.63,

3.81)

0.34

Table 84. Relative Risk of Infection - Placebo vs. Preoperative Antibiotics

Level of

Evidence Author N Joint

Duration

(years)

Relative

Risk*

(95%

CI)

Positive

Likelihood

Ratio

(95% CI)

Negative

Likelihood

Ratio

(95% CI)

Number

Needed

to Treat

II Carlsson 171 Hip 0.5

∞ (no

infections

in

antibiotic

group)

1.99

(1.71,

2.31)

0 22

II Carlsson 118 Hip 5

7.2

(1.7,

30.5)

2.03

(1.52,

2.71)

0.22

(0.06,

0.81)

5

II Doyon 2137 Hip 2 3.5

(1.7, 7.1)

1.58

(1.34,

1.85)

0.44

(0.25,

0.76)

43

II Doyon 1069 Hip 5 4.9

(2.5, 9.6)

1.73

(1.52,

1.97)

0.33

(0.18,

0.57)

14

* RR > 1 indicates greater risk in placebo group


205

Table 85. Registry Data – Hazard Ratio of Revision due to Infection

Level of

Evidence Author N

Type of

Surgery Joint Adjusted Hazard Ratio*

II

Jamsen

(<25 patients in

the no antibiotic

group)

2166 Revision Knee

systemic + cement: 1

systemic only: 2.1 (1.1, 3.9)

cement only: 1.9 (0.5, 7.7)

neither: 3.4 (0.8, 14.5)

II Engesaeter 22170 Primary Hip

systemic + cement: 1

systemic only: 1.8 (1.1, 3.0)

cement only: 2.7 (0.8, 8.7)

neither: 4.9 (1.2, 20.2)

*Jamsen adjusted for age, gender, diagnosis, type of implanted prosthesis;

Engesaeter adjusted for age, sex, cement and prosthesis brand, type of operating theatre,

operating time


206

FUTURE RESEARCH While many of the recommendations in this guideline are supported by high quality

evidence, certain areas are still lacking in high quality evidence. A number of diagnostic

tests exist and no single test has yet been identified that consistently allows the clinician

to rule in or rule out the presence of a periprosthetic infection in all patients. Given the

potential problems with instituting treatment and missing this diagnosis, future research

in the area of diagnosing a periprosthetic joint infection is warranted.

Specifically, further studies that characterize facets of the patient’s history and physical

examination as well as the presence of comorbidities that may affect the probability of a

periprosthetic joint infection are needed to help guide diagnostic algorithms.

Molecular techniques to aid in the diagnosis of PJI are currently under investigation. This

includes the use of microarrays, the polymerase chain reaction (PCR), proteomics, and

ELISA for measuring various cytokines, enzymes, IL-6, and neutrophil enzymes.The

routine role of sonification of removed implants and cement spacers also needs to be

clarified. At the time of publication of these guidelines, there are inconclusive results to

recommend the use or cost-effectiveness of these tests in clinical practice. Thus, further

studies are needed to determine their utility.

While there was strong evidence to support the use of an erythrocyte sedimentation rate

and c-reactive protein as initial screening tests for infection, the value of these tests for

patients with inflammatory arthritis (such as rheumatoid arthritis) or other systemic

diseases associated with increased ESR and CRP levels is unclear.

There is currently inadequate evidence to support or refute the role of wound swab in

management of patients with suspected periprosthetic joint infection. The efficacy of

various tests at the second stage of a two-stage operation for known periprosthetic

infection also requires clarification.

Patients who present with a painful total hip or total knee arthroplasty, who do not

otherwise have a clear indication for reoperation or revision, also present a diagnostic

challenge as cultures from the joint may be difficult or impossible to obtain. Further,

analysis of the value of non-invasive testing modalities, that do not rely on direct

sampling from around the prosthesis (such as advance imaging studies) would be of

value.

Finally, the effect that antibiotic treatment has on the utility of many of the commonly

used tests for diagnosing a periprosthetic joint infection is incompletely understood.

Many patients suspected of a periprosthetic joint infection may have received prior

treatment with antibiotics and the temporal effect of such treatment is unclear. While the

work group issued a strong recommendation against the administration of antibiotics

prior to obtaining a culture from the joint, many patients unfortunately have had such

treatment by the time they are evaluated by an Orthopaedic surgeon adding to the

diagnostic challenge. Finally, while the benefits of prophylactic antibiotics prior to the

surgical incision for preventing surgical site infections is clear, the benefit of withholding

such antibiotic prophylaxis prior to obtaining deep cultures at the time of re-operation or


207

revision is unclear, and future studies that examine the effect of a single prophylactic

dose of antibiotics on the sensitivity of operative cultures are warranted.


208

V. APPENDIXES


209

APPENDIX I WORK GROUP

Craig Della Valle MD, Chair


1611 W Harrison St # 300

Chicago, IL 60612-4861

Javad Parvizi, MD, Vice-Chair

Rothman Institute

925 Chestnut St - 5th Fl

Philadelphia, PA 19107

Thomas W Bauer, MD PhD

Cleveland Clinic Foundation

Department of Pathology

9500 Euclid Ave Desk L25

Cleveland, OH 44195

Paul E DiCesare, MD

UC Davis Medical Center

Department of Orthopaedic Surgery

4860 Y St Ste 3800

Sacramento, CA 95817

Richard Parker Evans, MD

University of Arkansas for Medical Sciences

Department of Orthopedics

4301 W Markham, #531

Little Rock, AR 72205

John Segreti, MD


600 S Paulina St. Ste 143

Chicago, Il 60612

Mark Spangehl, MD

Mayo Clinic

5777 East Mayo Blvd

Phoenix, AZ 85054

Guidelines and Technology Oversight

Chair:

William C. Watters III MD 6624 Fannin #2600

Houston, TX 77030

Evidence Based Practice Committee Chair:

Michael Keith, MD

2500 Metro Health Drive

Cleveland, OH 44109-1900

AAOS Staff:

Charles M. Turkelson, PhD Director of Research and Scientific Affairs

6300 N River Road

Rosemont, IL 60018

Janet L. Wies MPH

AAOS Clinical Practice Guideline Mgr

Patrick Sluka MPH

AAOS Research Analyst

Kristin Hitchcock

AAOS Medical Librarian

Special Acknowledgements

Sara Anderson MPH

Kevin Boyer

Laura Raymond, MA


210

APPENDIX II AAOS BODIES THAT APPROVED THIS CLINICAL PRACTICE GUIDELINE

Guidelines and Technology Oversight Committee

The AAOS Guidelines and Technology Oversight Committee (GTOC) consists of sixteen

AAOS members. The overall purpose of this Committee is to oversee the development of

the clinical practice guidelines, performance measures, health technology assessments

and utilization guidelines.

Evidence Based Practice Committee

The AAOS Evidence Based Practice Committee (EBPC) consists of ten AAOS members.

This Committee provides review, planning and oversight for all activities related to

quality improvement in orthopaedic practice, including, but not limited to evidence-based

guidelines, performance measures, and outcomes.

Council on Research, Quality Assessment, and Technology

To enhance the mission of the AAOS, the Council on Research, Quality Assessment, and

Technology promotes the most ethically and scientifically sound basic, clinical, and

translational research possible to ensure the future care for patients with musculoskeletal

disorders. The Council also serves as the primary resource to educate its members, the

public, and public policy makers regarding evidenced-based medical practice,

orthopaedic devices and biologics, regulatory pathways and standards development,

patient safety, occupational health, technology assessment, and other related areas of

importance.

The Council is comprised of the chairs of the AAOS Biological Implants, Biomedical

Engineering, Evidence Based Practice, Guidelines and Technology Oversight,

Occupational Health and Workers’ Compensation, Patient Safety, Research

Development, and US Bone and Joint Decade committees. Also on the Council are the

AAOS second vice-president, representatives of the Diversity Advisory Board, the

Women's Health Issues Advisory Board, the Board of Specialty Societies (BOS), the

Board of Councilors (BOC), the Communications Cabinet, the Orthopaedic Research

Society (ORS), the Orthopedic Research and Education Foundation (OREF), and three

members at large.

Board of Directors

The 17 member AAOS Board of Directors manages the affairs of the AAOS, sets policy,

and determines and continually reassesses the Strategic Plan.


211

DOCUMENTATION OF APPROVAL

AAOS Work group Draft Completed November 25, 2009

Peer Review Completed December 28, 2009

Public Commentary Completed April 15, 2010

AAOS Guidelines and Technology Oversight Committee April 24, 2010

AAOS Evidence Based Practice Committee April 24, 2010

AAOS Council on Research Quality Assessment May 17, 2010

and Technology

AAOS Board of Directors June 18, 2010


212

APPENDIX III STUDY ATTRITION FLOWCHART

6873 abstracts screened

for inclusion

459 articles recalled for

full text review

6414 abstracts excluded

105 articles recalled from

bibliography screening

473 articles excluded

91 articles included


213

APPENDIX IV LITERATURE SEARCHES

Search Strategy for PubMed

(periprosthetic[tiab] OR "Arthroplasty, Replacement, Hip"[Mesh] OR "Arthroplasty,

Replacement, Knee"[Mesh] OR "Hip Prosthesis"[mh] OR "Knee Prosthesis"[mh]

OR ((hip[tiab] OR "Hip Joint"[mh] OR knee[tiab] OR "Knee Joint"[mh] OR

acetabular[tiab] OR femoral[tiab] OR tibial[tiab] OR patellar[tiab])

AND (arthroplasty[tiab] OR implant[tiab] OR implants[tiab] OR "total joint"[tiab] OR

unicompartment*[tiab] OR replacement[tw] OR resurfacing[tiab] OR

hemiarthroplasty[tiab] OR component[tiab] OR (cup[tiab] AND stem[tiab]) OR

revision[tiab] OR resection[tiab] OR prosthesis[tiab] OR prostheses[tiab] OR

prosthetic[tiab] OR "Joint Prosthesis"[mh] OR "Prosthesis Failure"[mh]))) AND

(("Prosthesis-Related Infections"[mh] OR infection[tiab] OR infected[tiab] OR

"Sepsis"[mh] OR sepsis[tiab] OR septic[tiab] OR "Bacterial Infections"[mh] OR

"Bacteria"[mh] OR staphylococcus[tw] OR bacteria*[tiab] OR mycobacteria*[tw] OR

fungal[tw] OR fungus[tw] OR "Mycoses"[mh] OR coagulase negative staph[tw] OR

streptococcus[tw] OR acid-fast bacillus[tw] OR afb[tiab] OR gram positive[tw] OR gram

negative[tw] OR staphylococcus epidermidis[tw] OR pus[tw] OR

"Suppuration"[mh:noexp] OR purulence[tw]) OR ((pain[tiab] OR painful[tiab] OR

"Pain"[mh:noexp] OR stiffness[tw] OR warmth[tw] OR effusion[tw] OR redness[tw] OR

swelling[tw] OR bacteremia[tw] OR candidemia[tw]) AND ("Postoperative

Complications/radiography"[mh] OR "Postoperative Complications/pathology"[mh]OR

x-ray[tiab] OR "Blood Cell Count"[mh] OR cbc[tw] OR "Blood Sedimentation"[mh] OR

sedimentation rate[tw] OR "Erythrocyte Aggregation"[mh] OR "C-Reactive Protein"[mh]

OR "c-reactive protein"[tw] OR serology[tw] OR "Biopsy, Needle"[mh] OR

aspiration[tiab] OR "frozen section*"[tw] OR histology[tw] OR "Diagnostic

Imaging"[mh] OR "Radiopharmaceuticals/diagnostic use"[mh] OR sulfur colloid[tw] OR

gallium[tw] OR indium-111[tw] OR fdg-pet[tw] OR technetium-99[tw] OR MRI[tw] OR

(ct[tiab] AND scan[tiab])))) AND English[lang] AND 1970:2009/08/10[dp] NOT

(comment[pt] OR editorial[pt] OR letter[pt] OR addresses[pt] OR news[pt] OR

"newspaper article"[pt] OR "case reports"[pt] OR "historical article"[pt])

Sorted by study type

#1 Systematic[sb]

#2 (randomized controlled trial[pt] OR controlled clinical trial[pt] OR "randomized

controlled trials as topic"[mh] OR random allocation[mh] OR double-blind method[mh]

OR single-blind method[mh] OR clinical trial[pt] OR "clinical trials as topic"[mh] OR

"clinical trial"[tw] OR ((singl*[tw] OR doubl*[tw] OR trebl*[tw] OR tripl*[tw]) AND

(mask*[tw] OR blind*[tw])) OR "latin square"[tw] OR placebos[mh] OR placebo*[tw]

OR random*[tw] OR research design[mh:noexp] OR "comparative study "[pt] OR

"evaluation studies as topic"[mh] OR "evaluation studies "[pt] OR "follow-Up


214

studies"[mh] OR "prospective studies"[mh] OR "cross-over studies"[mh] OR

control*[tw] OR prospectiv*[tw] OR volunteer*[tw])

NOT #1 OR #2

Search strategy for EMBASE

(‘hip arthroplasty’/de OR ‘total hip prosthesis’/de OR ‘acetabuloplasty’/de OR ‘knee

arthroplasty’/de OR ‘total knee replacement’/de) AND

((‘infection’/de OR ‘gram negative infection’/de OR ‘gram negative sepsis’/de OR

‘staphylococcus infection’/de OR ‘streptococcus infection’/de OR ‘mycosis’/exp OR

‘infection control’/de OR ‘infection rate’/de OR ‘infection prevention’/de OR ‘infection

risk’/de OR ‘bacterial infection’/exp OR ‘postoperative infection’/de OR ‘prosthesis

infection’/de)

OR ((pain OR painful OR stiffness OR warmth OR effusion OR redness OR swelling OR

bacteremia/de OR candidemia/de) AND (‘hip radiography’/de OR ‘knee radiography’/de

OR ‘frozen section’/de OR ‘blood cell count’/de OR ‘erythrocyte sedimentation rate’/de

OR ‘c reactive protein’/de OR ‘aspiration biopsy’/de OR ‘joint aspiration’/de OR

‘nuclear magnetic resonance’/exp OR ‘computer assisted tomography’/exp OR

‘diagnostic imaging’/de OR ‘radiopharmaceutical agent’/exp)))

AND ([article]/lim OR [conference paper]/lim OR [review]/lim) AND [english]/lim

AND [embase]/lim


#1 'meta analysis' OR 'systematic review' OR medline

#2 random* OR 'clinical trial' OR 'health care quality'/exp

NOT #1 OR #2

Search strategy for CINAHL

((MM “Arthroplasty, Replacement, Hip” or MM “Arthroplasty, Replacement, Knee” or

((hip or knee) and (replacement* or prosthesis or prostheses or implant*))) AND

(infection or infected or MM infection+ or MM mycoses+ or MM “Prosthesis-Related

Infections” or MM “Bacterial Infections+” or MM Streptococcus+ or MM

Staphylococcus+ or MM “Staphylococcal Infections” or MM “Streptococcal Infections+”

or MM Sepsis+ or MM Suppuration))

and PT “research” and LA English and PY 1970-2009

NOT

PT “editorial” or PT “letter” or PT “case study” or MM “case studies”


215


#1 (MM “meta analysis” or MM “systematic review” or PT “systematic review”)

NOT (#1)

Search strategy for Cochrane Central

(joint):ti,ab,kw and (arthroplasty OR prosthesis OR prosthetic OR replacement OR

implant):ti,ab,kw and (hip OR knee OR acetabular):ti,ab,kw and (infection OR

infected):ti,ab,kw


216

APPENDIX V DATA EXTRACTION ELEMENTS

The data elements below were extracted into electronic forms in Microsoft® Excel. The

extracted information includes:

Study Characteristics

Selection criteria

Reference standard details

Index test details

Blinding of index test results when interpreting reference standard

Blinding of reference standard results when interpreting index test

Withdrawals from study

Results

True positives

True negatives

False positives

False negatives

Uninterpretable/intermediate results


217

APPENDIX VI JUDGING THE QUALITY OF DIAGNOSTIC STUDIES

The QUADAS tool108-110

is used to identify sources of bias, variability, and the quality of

reporting in studies of diagnostic accuracy. Fourteen questions answered “yes”, “no”, or

“unclear” contribute to the QUADAS tool. There is no score derived from the use of the

QUADAS tool.

Was the spectrum of patient’s representative of the patients who will receive the test in

practice?

Were selection criteria clearly described?

Is the reference standard likely to correctly classify the target condition?

Is the time period between ref. standard and index test short enough to be reasonably sure

that the target condition did not change between the two tests?

Did the whole sample or a random selection of the sample, receive verification using a

reference standard of diagnosis?

Did patients receive the same reference standard regardless of the index test result?

Was the reference standard independent of the index test (i.e. the index test did not form

part of the reference standard)?

Was the execution of the index test described in sufficient detail to permit replication of

the test?

Was the execution of the reference standard described in sufficient detail to permit its

replication?

Were the index test results interpreted without knowledge of the results of the reference

standard?

Were the reference standard results interpreted without knowledge of the results of the

index test?

Were the same clinical data available when test results were interpreted as would be

available when the test is used in practice?

Were uninterpretable/intermediate test results reported?

Were withdrawals from the study explained?


218

JUDGING THE QUALITY OF PROGNOSTIC STUDIES

Were the variables of interest clearly identified in the Methods section?

Were all variables of interest discussed in the Results section?

Were there sufficient patients per variable?

Were there sufficient events per variable?

If coding of variables is used, is the coding scheme described or unambiguous?

Collinearity has been tested or there is no obvious potential for collinearity?

Was the fitting procedure explicitly stated?

Were any goodness-of-fit statistics reported?

Was the model subjected to a test of validation?

JUDGING THE QUALITY OF TREATMENT STUDIES

RANDOMIZED CONTROLLED TRIALS

Did the study employ stochastic randomization?

Was there concealment of allocation?

Were subjects blinded to the treatment they received?

Were those who assessed/rated the patient’s outcomes blinded to the group to which the

patients were assigned?

Was there more than 80% follow-up for all patients in the control group and the

experimental group on the outcome of interest?

Did patients in the different study groups have similar levels of performance on ALL of

the outcome variables at the time they were assigned to groups?

For randomized crossover studies, was there evidence that the results obtained in the

study’s two experimental groups (in period 1 and 2) did not differ?

For randomized crossover studies, was there evidence that the results of the two control

groups (in period 1 and 2) did not differ?


219

APPENDIX VII FORM FOR ASSIGNING STRENGTH OF RECOMMENDATION

(INTERVENTIONS)

GUIDELINE RECOMMENDATION___________________________________

PRELIMINARY STRENGTH OF RECOMMENDATION: ________________

STEP 1: LIST BENEFITS AND HARMS

Please list the benefits (as demonstrated by the systematic review) of the intervention.

Please list the harms (as demonstrated by the systematic review) of the intervention.

Please list the benefits for which the systematic review is not definitive.

Please list the harms for which the systematic review is not definitive.

STEP 2: IDENTIFY CRITICAL OUTCOMES

Please circle the above outcomes that are critical for determining whether the intervention

is beneficial and whether it is harmful.

Are data about critical outcomes lacking to such a degree that you would lower the

preliminary strength of the recommendation?

What is the resulting strength of recommendation?

STEP 3: EVALUATE APPLICABILITY OF THE EVIDENCE

Is the applicability of the evidence for any of the critical outcomes so low that

substantially worse results are likely to be obtained in actual clinical practice?

Please list the critical outcomes backed by evidence of doubtful applicability.

Should the strength of recommendation be lowered because of low applicability?


STEP 4: BALANCE BENEFITS AND HARMS

Are there trade-offs between benefits and harms that alter the strength of

recommendation obtained in STEP 3?



220

STEP 5 CONSIDER STRENGTH OF EVIDENCE

Does the strength of the existing evidence alter the strength of recommendation obtained

in STEP 4?


NOTE: Because we are not performing a formal cost analyses, you should only consider

costs if their impact is substantial.


221

APPENDIX VIII VOTING BY THE NOMINAL GROUP TECHNIQUE

Voting on guideline recommendations will be conducted using a modification of the

nominal group technique (NGT), a method previously used in guideline development.71

Briefly each member of the guideline workgroup ranks his or her agreement with a

guideline recommendation on a scale ranging from 1 to 9 (where 1 is “extremely

inappropriate” and 9 is “extremely appropriate”). Consensus is obtained if the number of

individuals who do not rate a measure as 7, 8, or 9 is statistically non-significant (as

determined using the binomial distribution). Because the number of workgroup members

who are allowed to dissent with the recommendation depends on statistical significance,

the number of permissible dissenters varies with the size of the workgroup. The number

of permissible dissenters for several workgroup sizes is given in the table below:

Workgroup Size Number of Permissible

Dissenters

≤ 3

Not allowed, statistical

significance cannot be

obtained

4-5 0

6-8 1

9 1 or 2

The NGT is conducted by first having members vote on a given recommendation without

discussion. If the number of dissenters is “permissible”, the recommendation is adopted

without further discussion. If the number of dissenters is not permissible, there is further

discussion to see whether the disagreement(s) can be resolved. Three rounds of voting are

held to attempt to resolve disagreements. If disagreements are not resolved after three

voting rounds, no recommendation is adopted.

OPINION-BASED RECOMMENDATIONS

A guideline can contain recommendations that are backed by little or no data. Under such

circumstances, work groups often issue opinion-based recommendations. Although doing

so is sometimes acceptable in an evidence-based guideline (expert opinion is a form of

evidence), it is also important to avoid constructing a guideline that liberally uses expert

opinion; research shows that expert opinion is often incorrect.

Opinion-based recommendations are developed only if they address a vitally important

aspect of patient care. For example, constructing an opinion-based recommendation in

favor of taking a history and physical is warranted. Constructing an opinion-based

recommendation in favor of a specific modification of a surgical technique is seldom

warranted. To ensure that an opinion-based recommendation is absolutely necessary, the


222

AAOS has adopted rules to guide the content of the rationales that underpin such

recommendations. These rules are based on those outlined by the US Preventive Services

Task Force (USPSTF).81

Specifically, rationales based on expert opinion must:

Not contain references to or citations from articles not included in the

systematic review that underpins the recommendation.

Not contain the AAOS guideline language “We Recommend”, “We suggest”

or “treatment x is an option”.

Contain an explanation of the potential preventable burden of disease. This

involves considering both the incidence and/or prevalence of the disease,

disorder, or condition and considering the associated burden of suffering. To

paraphrase the USPSTF, when evidence is insufficient, provision of a

treatment (or diagnostic) for a serious condition might be viewed more

favorably than provision of a treatment (or diagnostic) for a condition that

does not cause as much suffering. The AAOS (like the USPSTF) understand

that evaluating the “burden of suffering” is subjective and involves judgment.

This evaluation should be informed by patient values and concerns. The

considerations outlined in this bullet make it difficult to recommend new

technologies. It is not appropriate for a guideline to recommend widespread

use of a technology backed by little data and for which there is limited

experience. Such technologies are addressed in the AAOS’ Technology

Overviews.

Address potential harms. In general, “When the evidence is insufficient, an

intervention with a large potential for harm (such as major surgery) might be

viewed less favorably than an intervention with a small potential for harm

(such as advice to watch less television).”81

Address apparent discrepancies in the logic of different recommendations.

Accordingly, if there are no relevant data for several recommendations and the

work group chooses to issue an opinion-based recommendation in some cases

but chooses not to make a recommendation in other cases, the rationales for

the opinion-based recommendations must explain why this difference exists.

Information garnered from the previous bullet points will be helpful in this

regard.

Consider current practice. The USPSTF specifically states that clinicians

justifiably fear that not doing something that is done on a widespread basis

will lead to litigation.81

The consequences of not providing a service that is

neither widely available nor widely used are less serious than the

consequences of not providing a treatment accepted by the medical profession

and thus expected by patients. Discussions of available treatments and

procedures rely on mutual communication between the patient’s guardian and

physician, and on weighing the potential risks and benefits for a given patient.

The patient’s “expectation of treatment” must be tempered by the treating


223

physician’s guidance about the reasonable outcomes that the patient can

expect.

Justify, why a more costly device, drug, or procedure is being recommended

over a less costly one whenever such an opinion-based recommendation is

made.

Work group members write the rationales for opinion based recommendations on the first

day of the final work group meeting. When the work group re-convenes on the second

day of its meeting, it will vote on the rationales. The typical voting rules will apply. If the

work group cannot adopt a rationale after three votes, the rationale and the opinion-based

recommendation will be withdrawn, and a “recommendation” stating that the group can

neither recommend for or against the recommendation in question will appear in the

guideline.

Discussions of opinion-based rationales may cause some members to change their minds

about whether to issue an opinion-based recommendation. Accordingly, at any time

during the discussion of the rationale for an opinion-based recommendation, any member

of the work group can make a motion to withdraw that recommendation and have the

guideline state that the work group can neither recommend for or against the

recommendation in question.

CHECKLIST FOR VOTING ON OPINION-BASED RECOMMENDATIONS

When voting on the rationale, please consider the following:

1. Does the recommendation affect a substantial number of patients or address

treatment (or diagnosis) of a condition that causes death and/or considerable

suffering?

2. Does the recommendation address the potential harms that will be incurred if it is

implemented and, if these harms are serious, does the recommendation justify;

a. why the potential benefits outweigh the potential harms and/or

b. why an alternative course of treatment (or diagnostic workup) that

involves less serious or fewer harms is not being recommended?

3. Does the rationale explain why the work group chose to make a recommendation

in the face of minimal evidence while, in other instances, it chose to make no

recommendation in the face of a similar amount of evidence?

4. Does the rationale explain that the recommendation is consistent with current

practice?

5. If relevant, does the rationale justify why a more costly device, drug, or procedure

is being recommended over a less costly one?


224

APPENDIX IX STRUCTURED PEER REVIEW FORM

Review of any AAOS confidential draft allows us to improve the overall guideline

but does not imply endorsement by any given individual or any specialty society

who participates in our review processes. The AAOS review process may result in

changes to the documents; therefore, endorsement cannot be solicited until the

AAOS Board of Directors officially approves the final guideline.

Reviewer Information:

Name of Reviewer_________________________________________

Address_________________________________________________

City___________________ State_________________ Zip Code___________

Phone _____________________Fax ________________________

E-mail_______________________

Specialty Area/Discipline: _______________________________________

Work setting: _________________________________________________

Credentials: _________________________________________________

May we list you as a Peer Reviewer in the final Guidelines? Yes No

Are you reviewing this guideline as Yes No

a representative of a professional society?

If yes, may we list your society as a reviewer Yes No

of this guideline?

Reviewer Instructions

Please read and review this Draft Clinical Practice Guideline and its associated Evidence

Report with particular focus on your area of expertise. Your responses are confidential

and will be used only to assess the validity, clarity, and accuracy of the interpretation of

the evidence. If applicable, please specify the draft page and line numbers in your

comments. Please feel free to also comment on the overall structure and content of the

guideline and Evidence Report.

If you need more space than is provided, please attach additional pages.

Please complete and return this form electronically to [email protected] or fax the form

back to Jan Wies at (847) 823-9769.

Thank you in advance for your time in completing this form and giving us your feedback.

We value your input and greatly appreciate your efforts. Please send the completed form

and comments by Month/Day/Year.

mailto:[email protected]


225


226

COMMENTS

Please provide a brief explanation of both your positive and negative answers in the

preceding section. If applicable, please specify the draft page and line numbers in your

comments. Please feel free to also comment on the overall structure and content of the

guideline and Evidence Report

OVERALL ASSESSMENT

Would you recommend these guidelines for use in practice? (check one)

Strongly recommend _______

Recommend (with provisions or alterations) _______

Would not recommend _______

Unsure _______

COMMENTS:

Please provide the reason(s) for your recommendation.


227

APPENDIX X PEER REVIEW PANEL

Participation in the AAOS peer review process does not constitute an endorsement


Peer review of the draft guideline is completed by an outside Peer Review Panel. Outside

peer reviewers are solicited for each AAOS guideline and consist of experts in the

guideline’s topic area. These experts represent professional societies other than AAOS

and are nominated by the guideline workgroup prior to beginning work on the guideline.

For this guideline, 14 outside peer review organizations were invited to review the draft

guideline and all supporting documentation. Eight of these societies participated in the

review of the guideline draft and five explicitly consented to be listed as a peer review

organization in this appendix.

The organizations that reviewed the document and consented to be listed as a peer

review organization are listed below:

American Association of Hip and Knee Surgeons

European Bone and Joint Infection Society

Knee Society

Musculoskeletal Infection Society

Society of Nuclear Medicine

Individuals who participated in the peer review of this document and gave their

consent to be listed as reviewers of this document are:

Thomas K. Fehring MD

Kevin L. Garvin MD

Arlen D. Hanssen MD

James I. Huddleston MD

Douglas R. Osmon MD

Christopher J. Palestro MD

Geert H.I.M. Walenkamp MD, PhD.

Barbara Weissman MD

The Society for Nuclear Medicine Standards Committee


228

PUBLIC COMMENTARY

A period of public commentary follows the peer review of the draft guideline. If

significant non-editorial changes are made to the document as a result of public

commentary, these changes are also documented and forwarded to the AAOS bodies that

approve the final guideline.

Public commentators who gave explicit consent to be listed in this document include the

following:

William Jiranek MD

Andrew H. Schmidt MD, Orthopaedic Trauma Association

Participation in the AAOS guideline public commentary review process does not

constitute an endorsement of the guideline by the participating organizations or the

individual listed nor does it is any way imply the reviewer supports this document.


229

APPENDIX XI INTERPRETING THE FOREST PLOTS

Throughout the guideline we use descriptive diagrams or forest plots to present data from

studies comparing a diagnostic test to a reference standard. In the example below, the

positive and negative likelihood ratios are the effect measures used to depict study

results. The horizontal line running through each point represents the 95% confidence

interval for that point. In this graph, the solid vertical line represents “no effect” where

the likelihood ratio is equal to one. The dashed line represents the value of a likelihood

ratio that indicates a large and conclusive change in the probability of disease.

For example, in the figure below the summary estimate (diamond) indicates a positive

likelihood ratio close to 10 and a negative likelihood ratio of between 0.2 and 0.5. This

result is statistically significant because the 95% Confidence Interval does not cross the

“no effect” line. Please note that summary measures are not reported in the plot if high

heterogeneity (>50%) was present.

StudyId

COMBINED

Lachiewicz

Williams

Mulcahy

Eisler

Malhotra

Barrack

Fink

Della Valle

Glithero

1 2 5 10

DLR POSITIVE

StudyId

COMBINED

Lachiewicz

Williams

Mulcahy

Eisler

Malhotra

Barrack

Fink

Della Valle

Glithero

1.1 .2 .5

DLR NEGATIVE


230

APPENDIX XII CONFLICT OF INTEREST

All members of the AAOS workgroup disclosed any conflicts of interest prior to the

development of the recommendations for this guideline. Conflicts of interest are

disclosed in writing with the American Academy of Orthopaedic Surgeons via a private

on-line reporting database and also verbally at the recommendation approval meeting.

Disclosure Items: (n) = Respondent answered 'No' to all items indicating no conflicts.

1=Board member/owner/officer/committee appointments; 2= Medical/Orthopaedic

Publications; 3= Royalties; 4= Speakers bureau/paid presentations;5A= Paid consultant;

5B= Unpaid consultant; 6= Research or institutional support from a publisher; 7=

Research or institutional support from a company or supplier; 8= Stock or Stock Options;

9= Other financial/material support from a publisher; 10= Other financial/material

support from a company or supplier.

Thomas W Bauer, MD, PhD: (Cleveland, OH): 2 (Journal of Bone and Joint Surgery -

American); 5A (Musculoskeletal Transplant Foundation; Osteotech; Smith & Nephew;

Stryker). Submitted on: 08/27/2008.

Craig J Della Valle, MD: 2 (Clinical Orthopaedics and Related Research; Journal of the

American Academy of Orthopedic Surgeons; SLACK Incorporated); 4 (Angiotech); 5A

(Zimmer); 5B (Biomet; Kinamed); 7 (Zimmer); 10 (Smith & Nephew; Stryker).

Submitted on: 08/17/2008.

Paul E DiCesare, MD: 5A (Stryker); 7 (Stryker). Submitted on: 08/11/2008.

Richard Parker Evans, MD: 1 (American Academy of Orthopedic Surgeons); 4

(DePuy, A Johnson & Johnson Company; Smith & Nephew; Cubist); 5A (DePuy, A

Johnson & Johnson Company; Smith & Nephew; Cubist); 5B (3M); 7 (National Institutes

of Health (NIAMS & NICHD); Biomet; Cubist). Submitted on: 12/07/2007 and last

confirmed as accurate on 04/17/2008.

Michael Warren Keith, MD: (n). Submitted on: 10/10/2007 at 08:42 AM and last

confirmed as accurate on 04/09/2008.

Javad Parvizi, MD: 1 (Smarttech LLC); 2 (Clinical Orthopaedics and Related Research;

Journal of Arthroplasty; Journal of Bone and Joint Surgery - American; Journal of Bone

and Joint Surgery - British; Journal of Orthopaedic Research; Journal of the American

Academy of Orthopedic Surgeons); 4 (Johnson & Johnson); 5A (Stryker; Smith &

Nephew); 7 (Stryker). Submitted on: 10/10/2007.

John Segreti, MD: (Chicago, IL): 4 (Johnson & Johnson; Merck; Pfizer; Wyeth; Cubist);

5A (Johnson & Johnson; Pfizer; Wyeth); 5B (Medtronic); 7 (Abbott; Bristol-Myers

Squibb; Health and Human Services; Merck; Cubist); 8 (Pfizer; Zimmer). Submitted on:

08/12/2008.


231

Mark J Spangehl, MD (Phoenix, AZ): (n). Submitted on: 08/12/2008.

William Charles Watters III, MD: 1 (North American Spine Society; Work Loss Data

Institute); 2 (The Spine Journal); 5A (Stryker; Intrinsic Therapeutics; MeKessen Health

Care Solutions). Submitted on: 10/09/2007 at 08:09 PM and last confirmed as accurate on

04/23/2008.


232

APPENDIX XIII REFERENCES

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(3) Banit DM, Kaufer H, Hartford JM. Intraoperative frozen section analysis in

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value of preoperative aspiration before total knee revision. Clin Orthop Relat Res

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