osteomyelitis: osteomyelitis: pathophysiology & treatment decisions clifford b. jones, md...
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Osteomyelitis:Osteomyelitis:Pathophysiology &
Treatment Decisions
Clifford B. Jones, MD
Original Author: Clifford B. Jones, MD; March 2004 Revised February 2007 & February 2011
“One Should Especially Avoid Such Cases if One has a Respectable
Excuse, for the Favorable Chances are Few and the Risks are Many….
….Besides, if a Man does not Reduce the Fracture, He will be Thought Unskillful. If He does Reduce It, He will bring the Patient
Nearer to Death than Recovery.”
Hippocratic Writings, New York, Pelican Books, 1978
Fracture Management Goals
1. Osseous Union
2. Restore Limb Function
3. Avoid Complications
Osteomyelitis Results in:
1. Reduction in limb function
2. Psychological & Social dysfunction
3. Increased cost
Hansen’s 7 DsConcerning Prolonged Orthopaedic Problems
Despair
Divorce
Destitute
Depression
Delinquency
Default
DeathSigvard Ted Hansen, 1997
Introduction• 350,000 long bone fxs/yr
• Infection risk varies:– Type I open – 10/1,000 infections– Type III open – up to 25%
Gustilo Open Fx ClassJBJS, 72A: 299-303, 1990
2%
7%
7%10-50%25-50%
Open Fractures
Type II Type IIIA
Type IIIB Type IIIB
Negative Biology of Open Fx
Contamination
Crushing
Stripping
Devascularization
Comminution
Blood SupplyRhinelander, CORR, 1974
Blood SupplyRhinelander, CORR, 1974
Normal - endosteal/medullary 2/3-3/4
internal external
Fracture - periosteal/external majority
internal external
Periosteal Blood Supply Important
Centripetal FlowRhinelander, CORR, 1974
Initial Emergent Treatment
dT
Antibiotics, IV
Reduce
Stabilize
Cover wound
Why infection risk high?
Infection risk ≈ Fracture type (soft tissue)
Open fx = Contamination (70% cx +)
Open fx = Infected fx > 8 hours
Cost AnalysisInfection
– Increase cost 16-21%/pt
– Increase hosp stay 36-50%/pt
Total Cost $ 271 million/yr
Definition• Group of conditions• “…presence of bacteria & an
inflammatory response causing progressive destruction of bone.”– Fears, RL, et al, 1998
• “…suppurative process in bone caused by a pyogenic organism”
– Pelligrini, VD, et al, 1996
Why destruction of bone matrix?
Proteolytic enzymes
Hyperemia
Osteoclasts
Do Not Delay Tx & Dx
Classification• Waldvogel, 1971
– Classification based on pathogenesis
• May, 1989– 5 parts, post-traumatic tibial osteomyelitis
• Cierny & Mader, 1985– 4 factors affecting outcome
– Host, site, extent of necrosis, degree of impairment
PathogenesisWaldvogel, 1971
1. Hematogenous
2. Contiguous focus of infection
3. Direct inoculation
AnatomicClassification(Cierny-Mader)
1985
I:I: II:II:
III:III: IV:IV:
Classification Break-Down
I. MedullaryEndosteal nidus, min soft tissue involvement, ? Sinus tract
II. SuperficialSurface of bone, usu 2° to soft tissue defect
III. LocalizedLocalized sequestra, usu sinus tract, Usu stable s/p excision
IV. DiffusePermeative process, combination of I/II/III, Usu Unstable s/p excision
Physiologic Classification(Cierny-Mader, 1985)
A-Host: Good immune system & delivery
B-Host: Compromised hostBL: locally compromised
BS: systemically compromised
BC: combined
C-Host: Requires suppressive or no TxMinimal disabilityTx worse than dz, not a surgical candidate
Clinical Staging(Cierny-Mader, 1985)
Anatomic Type + Clinical StagePhysiologic ClassExample: IV BS tibial osteomyelitis = diffuse tibial lesion in a systemically compromised
host
Types of Pathophysiology
Acute/Hematogenous
Chronic/Nonhematogenous
Acute/Hematogenous
• Anatomy (Hobo)– Sharp twist in metaphyseal capillaries
• Stasis (Trueta)– Decreased flow in capillaries & veins
• Combination (Morrissy)– Trauma & Bacteria
Acute/HematogenousProgression of Dz
• Cell death 2° to bacterial exotoxins bacterial culture medium worsens condition
Vascularity, leukocytosis, edema Pressure w/in rigid osseous container Pain, swelling, erythemaPotential for septic arthritis (knee, hip, shoulder)
Chronic/Nonhematogenous
S. aureus ↑
Pseudomonas aureginosa ↑
Enterobacter
> 30% Polymicrobial> 30% Polymicrobial
Clinical Findings (varied)
Erythema
Swelling
Sinus Tract
Drainage
Limp
Fluctuence
NoneNone
PainPain
TendernessTenderness
FeverFever
HAHA
Nausea/VomitingNausea/Vomiting
Clinical Findings• Must have high index of suspicion
• Inappropriate use of Abx – obscure Sx
• Must obtain Dx quickly– If Tx started < 72°:
• Decrease incidence of chronic osteomyelitis
• Decrease destruction of bone
Laboratory DataAcute (Morrey, BF, OCNA, 1975)
WBC (25% of time)
– Abnormal differential, Left Shift (65%)
– Blood Cx – 50% positive
Chronic
– Mild anemia, WESR, C-reactive protein
– Possible leukocytosis with L shift
– Blood Cx – usually negative
Radiographs
Early – usu negative
Changes – delayed (10-21 days)
RadiographsSoft Tissue
– Swelling, obscured soft tissue planes, haziness
Osseous– Hyperemia, demineralization
– Lysis (when > 40% resorbed)
– Periosteal reaction
– Sclerosis (late)
Radionucleotide Imaging
99M Tc
67Ga
111In WBC
99M Tc
• Action
– binds to hydroxyapetite crystals
• Osteoblastic activity
– Demineralized bone
– Immature collagen
99M Tc• 3 Phase Bone Scan
1. Radionucleotide angiogram
2. Immediate post injection blood pool
3. Three hour: soft tissue, urinary excretion
• Diagnosis– Cellulitis: Phases 1 &2, no change 3– Osteomyelitis: Phases 1 & 2, focal 3
• Results: 94% sensitivity, 95% specificity– Rosenthal 1992, Schauwecker 1992
Cellulitis
Osteomyelitis
99M Tc: False Positive
DM foot d/o
Septic arthritis
Inflammatory bone dz
Adjacent to pressure sores
99M Tc
4 Phase Bone Scan• New development
• Action:
– Mature bone: uptake stops at 4 hr
– Immature woven bone: cont’d uptake at 24 hr
• Problem: needs f/u imaging at 24 hr (compliance)• Gupta 1988, Israel 1987, Schauwecker 1992
67Ga
• Exudation of in vivo labeled serum protein– Transferrin, haptoglobin, albumin
• Results– 81% sensitivity, 69% specificity– Schauwecker, 1992
• Combination with Tc sensitivity, but specificity
111In WBC
• Used in combination (Seabold, 1989)– In/Tc: 88% accurate– Ga/Tc: 39% accurate
• Preparation problem rad dose to spleen, 18-24hr delay
• Spine (Whalen, Spine 1991)– 83% false negative use MRI
MRINo radiation
Good soft tissue imaging
Imaging:– T1 Dark– T2 Bright/Mixed
T1 bright T2 dark
T1 bright T2 dark
MRI• Acute:
marrow fat granulation tissue H2O
• Chronic: thickened cortex– Low signal on all scans
• Cellulitis: no marrow changes
MRI ResultsSchauwecker, 1992
• Sensitivity 92-100%
• Specificity 89-100%
• Excellent for Spine (Modic, RCNA, 1986)– Sens 96%, Spec 92%, Accuracy 94%
• Soft tissue extension
• Sinus tract formation– Bright Tx from skin to bone
CT ImagingImage cortical and cancellous bone
Evaluate osseous adequacy of debridement
Aspiration BiopsyAcute
– Good, only 10-15% false negative
Chronic– Sinus tract cx: 76% sens, 80% spec– 70% with S aureus & Enterococcus– 30% Pseudomonas– Does not determine correct Abx
Acute/Hematogenous
Changing Bacterial Pathogens
Resistant Bacterium - ESKAPE
E Enterococcus faecuim
S Staphlococcus aureus
K Klebsiella pneumoniae
A Acinobacter baumannii
P Pseudomonas aeruginosa
E Enterobacter aerogenes
MSSA & MRSA
• MSSA Change to β lactam
• MRSA Treat ≤ MIC
Gram Negative Rods - SPICE
S Serratia
P Pseudomonas
I Indole positive
C Citrobacter
E Enterobacter
Gram Negative
Rods
Proionibacterium acnes• Axillary bacteria (sebaceous glands)
• Treated with:– 1st: PCN or vanco– 2nd: Macrolides & Fluoroquinolones
• Long incubation time
• Call lab – culture 2 wks, gram positive rods
• Especially important for shoulder:– Nonunions– Infections
Multilocus Polymerase Chain reaction & Electrospray Ionization/Mass Spectrometry
• Bacterial or fungal DNA is amplified by polymerase chain reaction and introduced into a mass spectroscopy by electrospray ionization
• The amplification procedure uses 16 S primers, and the primers can be varied to detect fungi and antibiotic resistance genes (eg, mec A).
Multilocus Polymerase Chain reaction & Electrospray Ionization/Mass Spectrometry
• Although culturing bacteria takes days, amplifying DNA takes hours
• Accurate, rapid point-of-care devices would be ideal for clinical use
Treatment Preventation
• Antibiotics – correct organism
• Debridement – until viable tissue obtained
• Irrigation
• Wound care/coverage
• Osseous & soft tissue stability– Fx stability– Dead space management
New Oral Agents: MRSA
Zyvox/linazid po/iv ↓ plts
Synercid iv
Infectious Disease Consult
Stability Oxymoron
Hardware increased ↑ bacterial growth
&
Fracture stability (hardware) ↓ bacterial growth
Glycocalyx = “slime”
Remove hardware, exchange for new once infection under controlRemove hardware, exchange for new once infection under control
Dead Space Control
Abx IMN Materials & Methods
Research: Retrospective Review
Time: 3 year period, 2 year F/U
Location: Level 1 Trauma Center
PatientsAge: 37 (range 18-67)
Femurs (n=4)
Closed n=2
Open n=2
Tibia (n=28)
Closed n=2
Open n=26
II: 4/26
IIIA: 12/26
IIIB: 10/28
10/28 open tibial fx with rotational or FTT for coverage
Antibiotic NailInserted Avg. 3 mo. (range 2 day – 23 mo.)
2 bags PMMA
2.O g Vancomycin
2.4 g Tobramycin
32 Fr Chest Tube
3.2 mm Guide Wire
Incise & Debride WoundI&D Wound
I&D Canal
Reamers, Vent Hole
Presentation
44 M44 M
4 bacterium4 bacterium
CoccidiomycosisCoccidiomycosis
2 prior known “flare ups”2 prior known “flare ups”
Antibiotic IMN
32 Fr Chest Tube2 bags PMMA2.0 Vancomycin2.4 Tobramycin
Insert under pressure into chest tube while still “wet”
Insert 3.2 mm ball tip guide rod
Remove plastic before PMMA too hot and melting plastic chest tube
Insert Abx IMN
Wait until IMN Insertion
Wound Healed
Labs Improved
Anabolic Host
Usually 4-8 wks
(Average 4-8 wks)(Average 4-8 wks)
Example
Infected Tibial Nonunion
• 32 M
• 2 ppd smoker
• MCA 18 mo, 2 prior surgeries
• Draining wound
• “No one to take care of him”– Translation No money
Presentation
Options
• Type IV BC
• Unstable with Osteo• Smoker, malnutrition• Local open wound
• Nothing• Revise with plate• Revise with nail• Revise with ex fix• Revise with Ilizarov• Amputation
Length +/-
Debridement of Skin & BoneDebridement of Skin & Bone
Dead Space Management
Stabilize NonunionStabilize Nonunion
Coverage of Wound
Lengthening Leg
Noncompliance - NonunionNoncompliance - Nonunion
Final – Healed with GraftingFinal – Healed with Grafting
Infected Tibial Nonunion
• 38 yo M
• Snuff tobacco
• 1 pint vodka/day
• 6 mo MCA with IIIB open tibia
Type I BS
Presentation
Initial Post opInitial Post op
3 mo
Exchange IMN at 4 ½ moExchange IMN at 4 ½ mo
Final at 18 moFinal at 18 mo
Example• 54 yo Male• Post-operative Pseudomonas osteomyelitis• Refractory to HW removal & Ancef• Healthy, non-smoking• Cierny III A Host
Photos from M Swiontkowski
Example 1
•Dead Space
•Calcaneal defect
Example 1• Debridement of all non-viable bone with
laser doppler
• Defect filled with antibiotic PMMA
• 6 wks antibiotics
Example 1, at 6 wks
• Removal Abx beads• Bone grafting• Lateral arm flap• Infection eradication
Example• 47 yo Male, smoker• Presentation 2 months s/p ORIF closed proximal
tibia fx• Draining wound• Exposed HW• Cierny III BC Host
• Photos from M Swiontkowski
Example
• Debridement
• HW remains
• Abx beads
Exposed plate
Example • Gastrocnemeus flap, STSG
Example • At 6 weeks
• Remove Abx beads
• Bone grafting
• Healed wound and fracture
Example• At 5 yo, tibial osteomyelitis• Partially treated• At 62 yo, presentation to MD• Chronic draining tibial osteomyelitis• Cierny III BC Host
• Photos from M Swiontkowski
Example•Sinus tracts
•Chronic skin changes
Example•I&D to normal bleeding bone with laser doppler
•Bx – negative for cancer
Example
• Abx beads
• Latissimus Flap
• STSG
Example• Removal Abx beads at 6 wks
• No bone graft – low demand patient
• Dz free at 8 years (70 yo)
The Fate of Patients with a “Surprise” Positive Culture
After Nonunion Surgery
Olszewski D, Stucken C, Tornetta III P, Ricci W, Struebel P, Jones C, Sietsema D
Results• 460 patients
• Two cohort groups
– 98 cultures (21%) “surprise” positive
– 362 cultures (79%) negative
BacteriaType of Bacteria Number
Coagulase-negative Staphylococcus 45
Methicillin-resistant S. Aureus 12
Pseudomonas 8
Proprionibacterium 8
Methicillin-sensitive S. Aureus 7
Bacillus 4
Peptostreptococcus 3
Staph species unspecified 3
Enterococcus 2
Strep viridans 2
Clostridium 2
E. coli, Staph epidermidis, Beta hemolytic strep,
Serratia, Candida and Aspergillus 1
Positive Cultures
• 98 with positive cultures
– 90 treated with antibiotics
• 6 – 8 week duration
• Culture specific
– 8 patients not treated
• “Presumed contaminant”
Union After Index
• Culture (+) = 66 / 90 (73%)
• Culture (-) = 347 / 362 (96%)
• P < 0.0001
Infection After Index
• Culture (+) = 11 / 90 (12%)
• Culture (-) = 15 / 362 (4%)
• P < 0.0001
Final Outcome• Culture (+) = 86 / 90 (95.5%)
– 24 Additional procedures – 9 / 13 Debridement only– 4 / 13 with 1 additional procedure– 4 / 90 (4.5%) infected nonunion– 2 BKA
• Culture (-) = 362 / 362 (100%)– 15 Additional procedures
• P < 0.0001
“Presumed Contaminants”• 8 “surprise” cultures not treated with antibiotics
– Deemed “contaminants”– 5 Healed– 3 Nonunions
• 1 Amputation
• 1 Infected nonunion
• 1 Non-infected nonunion
Culture Positive Culture Negative
Healed 73% 95.8%
Infected Nonunion
13% 4%
Additional Procedures
27% 4%
Union at final follow-up
93% 100%
All Patients
Summary
• 21% of 460 “at risk” nonunions had surprise positive culture
• Staph species
• 90 of 98 treated with antibiotics
Summary• Culture positive
–73% Index
–93% Final• Culture negative
–95.5% Index
–100% Final
“Surprise” cultures• Revision shoulder arthroplasty
– 17 to 29% “surprise” positives– 13 to 25% require re-revision
• Revision hip arthroplasty – 11% “surprise” positives– 13% require re-revision
1. Kelly II JD, Hobgood ER. Positive culture rate in revision shoulder arthroplasty. Clin Orthop Relat Res. 2009;467:2243-48.2. Topolski MS, Chin PY, Sperling JW, Cofield RH. Revision shoulder arthroplasty with positive intraoperative cultures: the value of preoperative
studies and intraoperative histology. J Shoulder Elbow Surg. 2006;15:402-406.3. Tsukayama DT, Estrada R, Gustilo RB. Infection after total hip arthroplasty: a study of the treatment of one hundred and six infections. J Bone
Joint Surg Am. 1996;78:512-523.
Conclusions• 21% “surprise” positive cultures
• 74% heal after initial index procedure
• 26% required additional procedures
Recommendations
• Counsel patients
• Treat all positive cultures
• Potentially offer two-stage procedures– Unknown efficacy– 79% would be unnecessary
Conclusion
Prevention
Early Dx
Early Tx
Stabilize
Convert to Union ASAP
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