topics in anaesthesia and critical...

Topics in Anaesthesia and Critical Care

H.K.F. VANVV SAENE, L. SILVESTRI, M.A. DE LA CAL (EDS)Infection Control in the Intensive Care Unit1998, 380 pp, ISBN 3-540-75043-6J. MILIC-EMILI (ED)Applied Physiology in Respiratory Mechanics1998, 246 pp, ISBN 3-540-75041-XG. GUARNIERI, F. ISCRA (EDS)Metabolism and Artificial Nutrition in the Critically III1999,130 pp, ISBN 88-470-0042-4J. MILIC-EMILI, U. LUCANGELO, A. PESENTI, W.A. ZIN (EDS)Basics of Respiratory Mechanism and Artificial Ventilation 1999, 268 pp, ISBN 88-470-0046-7M. TIENGO, Y.A. PALADINIPP , N. RAWAL (EDS)Regional Anaesthesia, Analgesia and Pain Management 1999, 362 pp, ISBN 88-470-0044-0I. SALVO, D. VIDYASAGAR (EDS)Anaesthesia and Intensive Care in Neonates and Children 1999,324 pp, ISBN 88-470-0043-2G. BERLOT, H. DTT ELOOZ, A. GULLO (EDS)Trauma Operative Procedures1999, 210 pp, ISBN 88-470-0045-9G.L. ATLEEAA , J.-L. VINCENT (EDS)Critical Care Cardiology in the Perioperative Period2000, 214 pp, ISBN 88-470-0133-1M.A. TIENGO (ED)Neuroscience: Focus on Acute and Chronic Pain2000, 214 pp, ISBN 88-470-0134-XH.K.F. VANVV SAENE, G. SGANGA, L. SILVESTRI (EDS)Infection in the Critically Ill: an Ongoing Challenge2001, 200 pp, ISBN 88-470-0138-2

Anestesia e Medicina Critica

G. SLAVICH (ED)Elettrocardiografia Clinica 1997, 328 pp, ISBN 3-540-75050-9G.L. ALATI, B. ALLARIA, G. BERLOT, A. GTT ULLO, A. LUZZANI,G. MARTINELLI, L. TORELLI (EDS)Anestesia e Malattie Concomitanti - Fisiopatologia e clinica del periodo perioperatorio1997, 381 pp, ISBN 3-540-75048-7B. ALLARIA, M. V. BALDASSARE, A. GULLO, A. LUZZANI,G. MANANI, G. MARTINELLI,A. PASETTOPP , L. TORELLI (EDS)Farmacologia Generale e Speciale in Anestesiologia Clinica1997, 312 pp, ISBN 88-470-0001-7A. GULLO (ED)Anestesia Clinica1998, 506 pp, ISBN 88-470-0038-6A. GULLO, L. GATTINONIMedicina Intensiva e Perioperatoria 2000, 863 pp, ISBN 88-470-0135-8A. GULLOMedicina Perioperatoria, Terapia Intensiva, Emergenza 2003, 604 pp, ISBN 88-470-0215-X

Vol.Infection Romane 1-02-2005 17:05 Pagina aginagina

H.K.F. van SaeneL. SilvestriM.A. De La CalInfection Control in the Intensive Care Unit

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113

H.K.F. van Saene (Editor)L. Silvestri (Editor)M.A. De La Cal (Editor)

Infection Controlin the IntensiveCare UnitSecond Edition

Series edited byAntonino Gullo

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il iH.K.F. Van Saene, M.D. L. Silvestri, M.D.Department of Medical Microbiology Emergency Department and UnitUniversity of Liverpool of Anesthesia and Intensive CareAlder Hey Children’s Hospital, NHS Trust Presidio Ospedaliero of GoriziaLiverpool, UK Gorizia, Italy

M.A. De La Cal, M.D.Department of Critical Care MedicineUniversity Hospital of GetafeMadrid, Spain

Series Topics in Anaesthesia and Critical Care edited byPROF. A. GULLO

Department of Perioperative Medicine, Intensive Care and EmergencyTTrieste University School of Medicine,TTrieste, Italy

Library of Congress Control Number: 2004114978

ISBN 88-470-0185-4 Springer Milan Berlin Heidelberg New York

TThis work is subject to copyright. All rights are reserved, whether the whole or part of thematerial is concerned, specifically the rights of translation, reprinting, reuse of illustrations,recitation, broadcasting, reproduction on microfilm or in any other way, and storage indata banks. Duplication of this publication or parts thereof is permitted only under theprovisions of the Italian Copyright Law in its current version, and permission for use mustalways be obtained from Springer. Violations are liable to prosecution under the ItalianCopyright Law.

Springer is a part of Springer Science+Business Mediaspringeronline.com© Springer-Verlag Italia 2005Printed in Italy

TThe use of general descriptive names, registered names, trademarks,etc. in this publicationdoes not imply, even in the absence of a specific statement, that such names are exemptfrom the relevant protective laws and regulations and therefore free for general use.Product liability: The publisher cannot guarantee the accuracy of any information aboutdosage and application contained in this book. In every individual case the user mustcheck such information by consulting the relevant literature.

Cover design: Simona Colombo, Milan, ItalyTTypesetting: Graphostudio, Milan, ItalyPrinting: Grafiche Porpora, Cernusco S/N, Italy

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fPreface

Seven years have passed since the first edition of ‘Infection Control in theIntensive Care Unit’ was published. That book was a compilation of the lecturesread at an intensive course on management of infection in the critically illorganised by Professor A. Gullo in Trieste, Italy, and has been completely rewrit-ten by Italian, Spanish, South American, Dutch and Anglo-Canadian authors inthis second edition. The book is up to date, with references to publications from2004. We regard it as important that all statements are justified by the best avail-able evidence. All authors have made efforts to avoid unsubstantiated expertopinion. Although prevention is not entirely separate from therapy, preventionrather than cure is pivotal in this publication.

There are five sections in this second edition. The first section deals withbasics in microbiology specifically as they operate in supporting infection con-trol. Surveillance cultures of throat and rectum are an integral part of themicrobiological approach of this publication. Surveillance cultures are required

fto determine the carrier state. Carriage is indispensable for the classification ofmicro-organisms into low level, high level pathogens and potentially pathogen-ic micro-organisms. This distinction is crucial as prevention methods targetonly potentially pathogenic micro-organisms and high level pathogens. Thefront cover illustrates the usefulness of classifying infections occurring on theintensive care unit [ICU], again using carriage as detected by surveillance cul-tures. Primary endogenous pneumonias are the main infectious problem on theICU, with an incidence of about 55%. Primary endogenous pneumonia causedby potential pathogens, both ‘normal’ and ‘abnormal’, usually occurs within aweek of admission to ICU. Previously healthy individuals including trauma andsurgical patients develop early endogenous pneumonias with the ‘normal’potential pathogens such as Streptococcus pneumoniae, Haemophilus influen-zae, Moraxella catarrhalis and Staphylococcus aureus. Patients with underlyingchronic conditions such as diabetes, alcoholism and chronic obstructive pul-monary disease and who are referred to the ICU from home or from otherwards and hospitals, may carry abnormal aerobic Gram-negative bacilli[AGNB] such as Klebsiella, Acinetobacter and Pseudomonas species in theiradmission flora. This type of patient may develop a primary endogenous pneu-monia with abnormal flora. Fortunately, most patients recover from their pri-mary endogenous pneumonia after intensive care treatment including antibiot-ic therapy. About one third of ICU admissions may develop a late pneumonia,

yusually after the first weeks’ treatment on ICU. These patients invariablyacquire abnormal AGNB, which are associated with the ICU-environment, intheir oropharynx. This leads to secondary carriage and oropharyngeal over-

Vol.Infection Romane 1-02-2005 17:06 Pagina V

growth, migration and colonisation/infection of the lower airways. Thissequence of events is termed secondary endogenous pneumonia because thepneumonia is preceded by oropharyngeal carriage. Finally, P. aeruginosa hasbeen described as possessing an intrinsic tropism to colonise lower airwaysrather than the oropharynx when both sites are equally accessible to bacterialentry. The pathogenesis of this type of pneumonia is termed exogenous becausethe lung is infected by P.aeruginosa after direct inoculation without previouscarriage. The incidence of exogenous lower airway infections is about 15%, andthis exogenous pneumonia can occur at any time during treatment on the ICU.A new chapter not present in the first edition is dedicated to the standard oper-ating procedure of surveillance cultures. How to process surveillance culturesin order to distinguish the ‘normal’ from the ‘abnormal’ carrier state isdescribed in a separate chapter.

The second section deals with antimicrobials both parenteral and enteral.The most recent systemic antibiotics are discussed. Enteral antimicrobials areoften old, but a new chapter on all aspects of enteral non-absorbable antimi-crobials is added to the new edition.

Section three deals with policies, infection control, antibiotic and deviceguidelines. A new addition is the chapter on evidence based infection control.For the first time, 57 outbreaks of infection on ICU - all using molecular tech-niques for outbreak analysis - are carefully analysed and one third found to bepolyclonal rather than, as expected, monoclonal. The four components - par-enteral, enteral antibiotics, hygiene and surveillance cultures as part of selectivedecontamination of the digestive tract - are discussed in a separate chapter.

Section four deals with the infections occurring on neonatal, paediatric andadult ICUs. Infections developing in a particular subset of patients includingthose with trauma, burns, liver transplant and AIDS are part of section four.Compared with the first edition, a new chapter on clinical virology in all threetypes of ICU is inserted. Therapy of infection is based on six principles [i] sur-veillance and diagnostic cultures to identify micro-organisms; [ii] immediateand adequate antibiotic treatment to sterilise the internal organs; [iii] thesource of potential pathogens requires elimination for recovery of the originalinfection and prevention of relapses and/or superinfections; [iv] the use of top-ical antimicrobials such as aerosolised antimicrobials to sterilise the lower air-ways; [v] removal or replacement of the foreign device such as the endotrachealtube; [vi] surveillance samples are indispensable to monitor efficacy of treat-ment. This approach – albeit not always evidence based – is described in a sep-arate chapter.

The last section comprises special topics such as nutrition, gut mucosal pro-tection, the role of the pharmacist in infection control and the control of multi-resistant AGNB and methicillin-resistant Staphylococcus aureus f. The addition ofenteral to parenteral antimicrobials has been shown to be an approach for thecontrol of antimicrobial resistance on the ICU. A five year experience is pre-sented. Evidence based maneuvres on the ICU are analysed in the final chapter.

Preface

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We are very grateful to Lynda Jones and Julie Owens for their superb secre-tarial assistance, to Ken Maddocks for his diagram on the cover page, to Prof.Antonino Gullo for his constructive suggestions, and to Donatella Rizza andCatherine Mazars from Springer for their loyal support.

This second edition is twice the length of the first edition. This is a drawbackbecause good books should be concise, but it is our aim to prune for the third

yedition in 2012. We hope that this book is instructive, is helpful in your dailyclinical practice and that you enjoy it.

H.K.F. van SaeneL. Silvestri

lM.A. de la Cal

VIIPreface

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Contents

SECTION ONEESSENTIALS IN CLINICAL MICROBIOLOGY

Chapter 1Glossary of Terms and DefinitionsR.E. SARGINSON, N. TAYLORTT , M.A. DE LA CAL, H.K.F. VAN SAENE . . . . . . . . . . . . . . 3

Chapter 2CarriageS. ROSSENEU, G. RIOS, P.E. SPRONK, J.J.M. VAN SAENE . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Chapter 3Colonization and InfectionL. SILVESTRI, G. MINO, H.K.F VAN SAENE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Chapter 4Classification of Micro-Organisms According to their PathogenicityM.A. DE LA CAL, E. CERDÀ, A. ABELLA, P. GARCIA-HIERRO . . . . . . . . . . . . . . . . . . . . . 49

Chapter 5Classification of ICU InfectionsL. SILVESTRI, M. VIVIANI, H.K.F. VAN SAENE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61

Chapter 6Gut Microbiology: Surveillance Samples for the Detectionof the Abnormal Carrier StateH.K.F VAN SAENE, G. IZQUIERDO, P. GARCIA-HIERRO, F. FONTANA . . . . . . . . . . . . . . 73

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SECTION TWOANTIMICROBIALS

Chapter 7Systemic AntibioticsA.R. DE GAUDIO, S. RINALDI, A. NOVELLI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

Chapter 8Systemic AntifungalsF. J. COOKE, T. ROGERS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

Chapter 9Enteral AntimicrobialsM. SANCHEZ, B.P. PIZER, S.R. ALCOCK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

SECTION THREEINFECTION CONTROL

Chapter 10 Evidence-Based Infection Control in the Intensive Care UnitJ. HUGHES, N. TAYLORTT , E. CERDÀ, M.A. DE LA CAL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191

Chapter 11Device PoliciesA.R. DE GAUDIO, A. DI FILIPPO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213

Chapter 12Antibiotic Policies in the Intensive Care UnitH.K.F. VAN SAENE, N.J. REILLY, A.YY DE SILVESTRE, G. NARDI . . . . . . . . . . . . . . . . . . . . . . 231

Chapter 13Outbreaks of Infection in Intensive Care Units-Usefulness of MolecularTechniques for Outbreak AnalysisV. DAMJANOVIC, X. CORBELLA, J.I. VAN DER SPOEL, H.K.F. VAN SAENE . . . . . . . . . . 247

Chapter 14Prevention of Infection Using Selective Decontaminationof the Digestive TractL. SILVESTRI, S. KERR, A. GULLO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297

Contents

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SECTION FOURINFECTIONS ON ICU

Chapter 15Lower Airway InfectionN. FÀBREGAS, A. ALCÓN, A. TORRES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315

Chapter 16Bloodstream Infections Including Endocarditis and MeningitisJ. VALLÉSVV , R. FERRER, P. FERNÁNDEZ-VILADRICH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337

Chapter 17Infections of the Peritoneum Including Pancreas, Mediastinum, Pleura,Wounds, and Urinary Tract G. SGANGA, G. BRISINDA, G. MARIA, M. CASTAGNETO . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379

Chapter 18Infection on the Neonatal and Pediatric Intensive Care UnitsA.J. PETROS, V. DAMJANOVIC, A. PIGNA, J. FARIASFF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415

Chapter 19Immediate Adequate Antibiotics control Morbidity and Mortality in Patients with Pancreatitis, Extensive Burns, Trauma, ExacerbatedChronic Obstructive Pulmonary Disease, or Liver TransplantationI. ALÍA, M.A. DE LA CAL, E. CERDÁ, H.K.F. VAN SAENE . . . . . . . . . . . . . . . . . . . . . . . . . . 429

Chapter 20Intensive Care Unit Patients following TransplantationA. MARTÍNEZ-PELLÚS, M. PALOMARPP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455

Chapter 21Clinical Virology in NICU, PICU and Adult ICUW. TONG, S. SCHELENZ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469

Chapter 22AIDS Patients in the Intensive Care UnitL. ALVAREZ-ROCHA, P. RASCADO-SEDES, J. PASTORPP -BENAVENT,TT

F. BARCENILLA-GAITE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495

Chapter 23Therapy of InfectionJ.H. ROMMES, A. SELBY, D.F. ZYY ANDSTRA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515

XIContents

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SECTION FIVESPECIAL TOPICS

Chapter 24SIRS, Sepsis, and MODSG. BERLOT, A. TTT OMASINI, M. VIVIANI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537

Chapter 25SIRS/Sepsis: Metabolic and Nutritional Changes and TreatmentF. ISCRA, A. RANDINO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549

Chapter 26Gut Mucosal Protection in the Critically Ill Patient.Towards an Integrated Clinical Strategy D. F. ZANDSTRA, P.H.J. VAN DER VOORT, K. TTT HORBURN, H.K.F. VAN SAENE . . . . 565

Chapter 27Selective Decontamination of the Digestive Tract:the Role of the PharmacistN.J. REILLY, A.J. NYY UNN, K. POLLOCK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 575

Chapter 28Antimicrobial Resistance: a Prospective 5-Year StudyH.K.F. VAN SAENE, N. TAYLORTT , N.J. REILLY, P.B. BYY AINES . . . . . . . . . . . . . . . . . . . . . . . . . 593

Chapter 29ICU-Acquired Infection: Mortality, Morbidity, and CostsJ.C. MARSHALL, K.A.M. MARSHALL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605

Chapter 30Evidence-Based Medicine in the Intensive Care UnitA.J. PETROS, K.G. LOWRY, H.K.F.YY VAN SAENE, J.C. MARSHALL . . . . . . . . . . . . . . . . . . . 621

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 635

XII Contents

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Abella A.Department of Critical Care Medicine, Hospital Universitario de Getafe,Madrid, Spain

Alcock S.R.Department of Bacteriology, Western Infirmary Glasgow, Glasgow, UK

Alcón A.Anesthesiology Department, Surgical Intensive Care Unit, URSC, Hospital Clínic,Universitat de Barcelona, Barcelona, Spain

Alía I.Department of Critical Care Medicine, Hospital Universitario de Getafe,Madrid, Spain

Alvarez-Rocha L.Intensive Care Unit, Juan Canalejo Hospital, Coruña, Spain

Baines P.B.Pediatric Intensive Care Unit, Alder Hey Children’s Hospital, Liverpool, UK

Barcenilla-Gaite F.Intensive Care Unit, Arnau de Vilanova Hospital, Lleida, Spain

Berlot G.Department of Anaesthesia, Perioperative Medicine, Intensive Care andEmergency, University Hospital School of Medicine, Trieste, Italy

Brisinda G.Surgery and Transplantation Unit, Policlinico Universitario Agostino Gemelli,Rome, Italy

Castagneto G.Surgery and Transplantation Unit, Policlinico Universitario Agostino Gemelli,Rome, Italy

Contributors

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Cerda E.Department of Critical Care Medicine, Hospital Universitario de Getafe,Madrid, Spain

Cooke F.J.Division of Microbiology, Hammersmith Hospital, London, UK

Corbella X.Department of Intensive Care, University of Barcelona, Barcelona, Spain

Damjanovic V.Department of Medical Microbiology, University of Liverpool,Liverpool, UK

De Gaudio A.R.Department of Anesthesia and Critical Care, University of Florence,Florence, Italy

de la Cal M.A.Department of Critical Care Medicine, Hospital Universitario de Getafe,Madrid, Spain

de Silvestre A.Department of Anaesthesia and Intensive Care, University Hospital ofS. Maria della Misericordia, Udine, Italy

Di Filippo A.Section of Anesthesiology and Intensive Care, Department of Critical Care,University of Florence, Florence, Italy

Fàbregas N.Anesthesiology Department, Surgical Intensive Care Unit, URSC, Hospital Clínic,Universitat de Barcelona, Barcelona, Spain

Farias J.Pediatric Intensive Care Unit, Children’s Hospital Ricardo Gutierrez,Buenos Aires, Argentina

Ferrer R.Intensive Care Department, Hospital Sabadell, Sabadell, Spain

Fernández-Viladrich P.F.Infectious Diseases Department, Hospital Bellvitge,Barcelona, Spain

XIV Contributors

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Fontana F.Department of Medical Microbiology, University Hospital of Gorizia,Gorizia, Italy

Garcia-Hierro P.Department of Medical Microbiology, University Hospital of Getafe,Madrid, Spain

Gullo A.Department of Perioperative Medicine, Intensive Care and Emergency, Universityof Trieste, Cattinara Hospital, Trieste, Italy

Hughes J.Department of Clinical Microbiology and Infection Control, University HospitalAintree, Liverpool, UK

Iscra F.Department of Perioperative Medicine, Intensive Care and Emergency,University of Trieste, Cattinara Hospital, Trieste, Italy

Izquierdo G.Department of Medical Microbiology, University of Trujillo, Peru

Kerr S.Department of Pediatric Intensive Care, Alder Hey Children’s Hospital,Liverpool, UK

Lowry K.G.Intensive Care Unit, Royal Victoria Hospital, Belfast, Northern Ireland

Maria G.Surgery and Transplantation Unit, Policlinico Universitario Agostino Gemelli,Rome, Italy

Marshall J.C.Department of Surgery, and Interdepartmental Division of Critical Care,General Hospital and University of Toronto, Toronto, Canada

Marshall K.A.M.Department of Surgery, and Interdepartmental Division of Critical Care,General Hospital and University of Toronto, Toronto, Canada

Martínez-Pellús A.Intensive Care Unit,Hospital Universitario Virgen de la Arrixaca,Murcia,Spain

XVContributors

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Mino G.Department of Bacteriology, University Hospital, Guayaquil, Ecuador

Nardi G.Department of Anesthesia and Intensive Care, University Hospital of S. CamilloForlanini, Rome, Italy

Novelli A.Department of Pharmacology, Florence University, Florence, Italy

Nunn A.J.Department of Pharmacy, Alder Hey Children’s Hospital, Liverpool , UK

Palomar M.Intensive Care Unit, Hospital Universitario Vall d’Hebrón,Barcelona, Spain

Pastor-Benavent J.Intensive Care Unit, Juan Canalejo Hospital, Coruña, Spain

Petros A.J.Pediatric Intensive Care Unit, Great Ormond Street Children’s Hospital, NHSTrust, London, UK

Pigna A.Neonatal Intensive Care Unit, San Orsola Hospital, Bologna, Italy

Pizer B.P.Department of Oncology, Alder Hey Children’s Hospital, NHS Trust,Liverpool, UK

Pollock K.Department of Pharmacy, Western Infirmary, Glasgow, UK

Randino A.Department of Perioperative Medicine, Intensive Care and Emergency,University of Trieste, Cattinara Hospital, Trieste, Ital

Rascado-Sedes P.Intensive Care Unit, Juan Canalejo Hospital, Coruña, Spain

Reilly N.J.Department of Pharmacy, Alder Hey Children’s Hospital,Liverpool, UK

XVI Contributors

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Rinaldi S.Department of Anesthesia and Critical Care, Florence University, Florence, Italy

Rios G.Department of Pediatric Intensive Care, Gustavo Fricke Children’s Hospital,Vina del Mar, Chile

Rogers T.Department of Clinical Microbiology, Trinity Centre, Dublin, Ireland

Rommes J.H.Department of Intensive Care, Gelre Ziekenhuizen, Apeldoorn, The Netherlands

Rosseneu S.Department of Pediatric Gastroenterology, Barts and the London NHS Trust,London, UK

Sanchez M.Department of Intensive Care, University Hospital of Principe de Asturias,Madrid, Spain

Sarginson R.E.Department of Anaesthesia and Intensive Care, Alder Hey Children’s Hospital,NHS Trust, Liverpool, UK

Schelenz S.Department of Infection, Guy’s and St. Thomas’ Hospital Trust and Departmentof Infectious Disease, GKT School of Medicine, St. Thomas’ Hospital,London, UK

Selby A.Department of Anaesthesia and Intensive Care, Alder Hey Children’s HospitalNHS Trust, Liverpool, UK

Sganga G.Surgery and Transplantation Unit, Policlinico Universitario Agostino Gemelli,Rome, Italy

Silvestri L.Emergency Department and Unit of Anesthesia and Intensive Care, PresidioOspedaliero of Gorizia, Gorizia, Italy

Spronk P.E.Department of Intensive Care, Gelre Ziekenhuizen, Apeldoorn, The Netherlands

XVIIContributors

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Taylor N.Department of Medical Microbiology, University of Liverpool, Liverpool, UK

Thorburn K.Department of Pediatric Intensive Care, Alder Hey Children’s Hospital, ,Liverpool, UK

Tomasini A.yDepartment of Perioperative Medicine, Intensive Care and Emergency, University

of Trieste, Cattinara Hospital, Trieste, Italy

Tong C.Y.W.Department of Infection, Guy’s and St. Thomas’ Hospital Trust and Departmentof Infectious Disease, GKT School of Medicine, St. Thomas’ Hospital,London, UK

Torres A.Institut Clínic de Pneumologia i Cirurgia Toràcica, Hospital Clínic,Universitat de Barcelona, Spain

Vallés J.Intensive Care Department, Hospital Sabadell, Sabadell, Spain

van der Spoel J.I.Department of Intensive Care, OLV Gasthuis, Amsterdam, The Netherlands

van der Voort P.H.J.Department of Intensive Care, Medical Center Leeuwarden,Leeuwarden, The Netherlands

van Saene H.K.F.Department of Medical Microbiology, University of Liverpool, Alder HeyChildren’s Hospital, NHS Trust, Liverpool, UK

van Saene J.J.M.Department of Pharmaceutical Technology, University of Groningen,Groningen, The Netherlands

Viviani M.yDepartment of Perioperative Medicine, Intensive Care and Emergency, University

of Trieste, Cattinara Hospital, Trieste, Italy

Zandstra D.F.Department of Intensive Care, Onze Lieve Vrouwe Gasthuis Hospital,Amsterdam, The Netherlands

XVIII Contributors

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ABELLA A., 49ALCOCK S.R., 171ALCÓN A., 315ALÍA I., 429ALVAREZ-ROCHA L., 495BAINES P.B., 593BARCENILLA-GAITE F., 495BERLOT G., 537BRISINDA G., 379CASTAGNETO G., 379CERDÀ E., 49, 191, 429COOKE F.J., 155CORBELLA X., 247DAMJANOVIC V., 247, 415DE GAUDIO A.R., 91, 213DE LA CAL M.A., 3, 49, 191, 429DE SILVESTRE A., 231DI FILIPPO A., 213FÀBREGAS N., 315FARIASFF J., 415FERNÀNDEZ-VILADRICH P.F., 337FERRER R., 337FONTANA F., 73GARCIA-HIERRO P., 49, 73GULLO A., 297HUGHES J., 191ISCRA F., 549IZQUIERDO G., 73KERR S., 297LOWRY K.G., 621MARIA G., 379MARSHALL J.C., 605, 621MARSHALL K.A.M., 605MARTÍNEZ-PELLÚS A., 455MINO G., 37NARDI G., 231NOVELLI A., 91

Authors’ Index

Vol.Infection Romane 1-02-2005 17:06 Pagina XIXginagina

NUNN A.J., 575PALOMARPP M., 455PASTORPP -BENAVENT J., 495PETROS A.J., 415, 621PIGNA A., 415PIZER B.P., 171POLLOCK K., 575RANDINO A., 549RASCADO-SEDES P., 495REILLY N.J., 231, 575, 593RINALDI S., 91RIOS G., 15ROGERS T., 155ROMMES J.H., 515ROSSENEU S., 15SANCHEZ M., 171SARGINSON R.E., 3SCHELENZ S., 469SELBY A., 515SGANGA G., 379SILVESTRI L., 37, 61, 297SPRONK P.E., 15TAYLORTT N., 3, 191, 593THORBURN K., 565TOMASINI A., 537TONG C.Y.W., 469TORRES A., 315VALLÉSVV J., 337VAN DER SPOEL J.I., 247VAN DER VOORT P.H.J., 565VAN SAENE H.K.F., 3, 37, 61, 73, 231, 247, 429, 565, 593, 621VAN SAENE J.J.M., 15VIVIANI M., 61, 537ZANDSTRA D.F., 515, 565

XX Authors Index

Vol.Infection Romane 1-02-2005 17:06 Pagina XXginagina

SECTION ONEESSENTIALS IN CLINICAL

MICROBIOLOGY

Vol.Infection/1 ok 1-02-2005 17:07 Pagina 1

Glossary of Terms and Definitions

R.E. SARGINSON, N. TAYLOR, M.A. DE LA CAL, H.K.F. VAN SAENE

Introduction

Definitions of terms are important to avoid ambiguity, particularly in an era ofglobal communication. Several words have often been used in an imprecisefashion in the past, including “sepsis”, “nosocomial”, “colonization”, and even“infection”. Although standardization in terminology is useful, frequent revi-sions will be needed in an era of rapid change in biomedical knowledge.

Definitions can be based on a variety of concepts, varying from abnormali-ties in patient physiology and clinical features to sophisticated laboratorymethods. A thoughtful introduction to clinical terminology can be found in theextensive writings of A.R. Feinstein [1, 2], who made use of set theory and Venndiagrams to categorize clinical conditions. The choice of boundaries betweensets or values on measurement scales can be difficult. In practice such bound-aries, which are used to differentiate between the presence, the absence, and/orthe severity of a condition, are often somewhat fuzzy, for example, in the diag-nosis of ventilator-associated pneumonia [3].

The situation is further complicated by considering problems in measure-ment and the timing of assessments. An apparently simple criterion such astemperature measurement is subject to variation in time, site, and technique ofmeasurement, together with errors from device malfunction, displacement, ormisuse. Most definitions of infection at various sites include fever as a neces-sary criterion, typically temperature ≥38.3oC. Do we have good evidence thatthis criterion is a reliable discriminator, in conjunction with other “necessary”criteria, in distinguishing the presence or absence of a particular type of infec-tion [4]?

Roger Bone raised some important issues a decade ago [5–8] for the terms“sepsis” and “inflammation”, a debate that continues. Other interestingapproaches in the fields of sepsis, the systemic inflammatory response, and

Chapter 1


multiple organ dysfunction are the use of “physiological state space” conceptsby Siegel et al. [9] and ideas from “complex adaptive system” and network the-ory [10–13].

The glossary described here forms a basis for our clinical practice in variousaspects of intensive care infection and microbiology. We advocate definitionsthat are usable in routine clinical practice and that emphasize the role of sur-veillance samples in classifying the origins of infection.

Terms and Definitions

Acquisition

A patient is considered to have acquired a micro-organism when a single sur-veillance sample is positive for a strain that differs from previous and subse-quent isolates. This is a transient phenomenon, in contrast to the more-persist-ent state of carriage.

Carriage/Carrier State

The same strain of micro-organism is isolated from two or more surveillancesamples in a particular patient. In practice, consecutive throat and/or rectalsurveillance samples taken twice a week (Monday and Thursday) yield identi-cal strains.

Normal carrier state. Surveillance samples yield only the indigenous aerobic andanaerobic flora, including Escherichia coli in the rectum. Varying percentages ofpeople carry “community” or “normal” potential pathogens in the throat and/orgut. Streptococcus pneumoniae and Hemophilus influenzae are carried in theoropharynx by more than half of the healthy population. Staphylococcus aureusand yeasts are carried in the throat and gut by up to a third of healthy people.

Abnormal carrier state. Opportunistic “abnormal” aerobic Gram-negative bacil-li (AGNB) or methicillin-resistant S. aureus (MRSA) are persistently present inthe oropharynx and/or rectum. MRSA and AGNB are listed under “hospital orabnormal micro-organisms”. E. coli, isolated from the oropharynx in high con-centrations (>3+ or >105 CFU/ml), also represents an abnormal carrier state.

Supercarriage (secondary carriage). Commonly used antibiotics eliminate “com-munity” or “normal” bacteria such as S. pneumoniae or H. influenzae, but pro-

4 R.E. Sarginson, N. Taylor, M.A. de la Cal, H.K.F. van Saene


mote the acquisition and subsequent carriage of abnormal AGNB and MRSA. Thisphenomenon is sometimes referred to as super or secondary carriage. Overgrowthwith micro-organisms of low pathogenicity, such as coagulase-negative staphylo-cocci and enterococci, can also occur during selective decontamination of thedigestive tract (SDD). Such organisms are not targeted by SDD protocols.

Central Nervous System Infections

This important group includes the terms meningitis, meningo-encephalitis,encephalitis, and ventriculitis and shunt infection. These conditions have someoverlap and may also co-exist with sinus or mastoid infections and septicemia.Microbiological diagnosis usually rests on culture of cerebrospinal fluid (CSF).Frequently, lumbar puncture is contraindicated in suspected meningitis [14].For example, in meningococcal infection, contraindications include a coagu-lopathy or where computed tomography (CT) scan features suggest a risk oftentorial pressure coning where lumbar puncture is to be performed. Alsoempirical antibiotics have frequently been started prior to hospital admission.These issues are particularly important in pediatric practice, where meningo-coccal DNA detection in blood and/or CSF by polymerase chain reaction [PCR]assays, together with bacterial antigen tests, improves diagnostic yield [15]. Theuse of molecular techniques including PCR in the detection of septicaemia incritically ill patients is still in the development stage but shows great promise[16]. The usual non-specific criteria of fever or hypothermia, leukocytosis orleukopenia, and tachycardia are present, with specific symptoms that mayinclude headache, lethargy, neck stiffness, irritability, fits, and coma. Cut-offvalues depend on age and should be defined at age-specific percentile thresh-olds for physiological variables, e.g., >90th percentile for heart rate. Detaileddefinitions would require a separate chapter!

Colonization

Micro-organisms are present in body sites that are normally sterile, such as thelower airways or bladder. Clinical features of infection are absent. Diagnosticsamples yield ≤1+ leukocytes per high power field [17] and microbial growth ishigh <3+ or <105 CFU/ml.

“Community”or “Normal” Micro-Organisms

These are micro-organisms carried by varying percentages of healthy people.These include S. aureus, S. pneumoniae, H. influenzae, Moraxella catarrhalis, E.coli, and Candida albicans.

Glossary of Terms and Definitions 5


Defense

Against carriage. The defense mechanisms of the oropharynx and gastrointesti-nal tract to prevent abnormal carrier states, e.g., fibronectin, saliva, and gastricsecretions.

Against colonization. The defense mechanisms of internal organs againstmicrobial invasion, e.g., the muco-ciliary elevator in the airways and secretedimmunoglobulins.

Against infection. The defense mechanisms of the internal organs, beyond skinand mucosa, include antibodies, lymphocytes, and neutrophils.

“Hospital” or “Abnormal” Micro-Organisms

These include micro-organisms carried by people with chronic disease or thoseadmitted to the intensive care unit (ICU) from in-patient wards or other hospi-tals. These are typically AGNB or MRSA. AGNB include Pseudomonas,Stenotrophomonas, Acinetobacter, Klebsiella, Enterobacter, Serratia, Proteus,and Morganella spp. These organisms are rarely carried by healthy people.

Infection

This can be remarkably difficult to define in clinical circumstances. Patients haveoften received empirical antibiotics. In principle, infection is a microbiological-ly proven, clinical diagnosis of local and/or generalized inflammation. Themicrobiological criteria conventionally include ≥105 CFU/ml of diagnostic sam-ple from the infected organ and ≥2+ leukocytes present per high-power field inthe sample. The thresholds chosen for clinical features and laboratory measure-ments depend on the age of the patient and the timing of assessment. These mayinclude temperature changes, heart rate, and changes in heart rate variability[10], white cell counts, C-reactive protein [18], and procalcitonin [19, 20].

Infections can be classified according to the concept of the carrier state [21].Primary endogenous infection is caused by micro-organisms carried by thepatient at the time of admission to the ICU, including both “normal” and“abnormal” micro-organisms.

Secondary endogenous infection is caused by micro-organisms acquired onthe ICU and not present in the admission flora. These micro-organisms usuallybelong to the “abnormal” group. Potentially pathogenic micro-organisms areacquired in the oropharynx, followed by carriage and overgrowth in the diges-tive tract. Subsequently colonization and then infection of internal organs mayoccur following migration or translocation across the gut mucosa into the lym-



phatics or bloodstream is possible.Exogenous infection is caused by micro-organisms introduced into the

patient from the ICU environment. Organisms are transferred directly, omittingthe stage of carriage, to a site where colonization and then infection occurs.

Inflammatory Markers

These are cells and proteins associated with the pro-inflammatory process.These include C-reactive protein [18], procalcitonin [19, 20], tumor necrosis fac-tor-α, interleukins-1 and -6 [22], lymphocytes, and neutrophils. The onset, mag-nitude, and duration of changes in these factors vary with site and severity ofinfection.

ICU Infection

ICU infection refers to secondary endogenous and exogenous infections –infections due to organisms not carried by the patient at the time of admissionto the ICU [23]. The term “nosocomial” (literally “related to the hospital”) is inwidespread use, but lacks a precise definition and should probably be aban-doned!

Intra-Abdominal Infection

This is an infection of an abdominal organ and of the peritoneal cavity (peri-tonitis). Peritonitis can be a local or general inflammation of the peritoneal cav-ity. Local signs such as tenderness and guarding may be difficult to elicit insedated ICU patients. Generalized, non-specific, features are fever (temperature≥38.3oC), leukocytosis (WBC >12,000/mm3) or leukopenia (WBC <4,000/mm3).Ultrasonography and/or CT evaluation may contribute to the diagnosis.Isolation of micro-organisms from diagnostic samples at a concentration of≥3+ or ≥105 CFU/ml, with ≥2+ leukocytes confirms the diagnosis. Specificexamples include fecal peritonitis due to colon perforation and peritonitis asso-ciated with peritoneal dialysis.

Isolation

Patients are nursed in separate cubicles or rooms, with strict hygiene measures,including protective clothing and hand washing, to control transmission ofmicro-organisms. These measures particularly apply to patients infected withhigh level pathogens or resistant micro-organisms and those with impairedimmunity.



Micro-Organisms

Micro-organisms can be ranked by pathogenicity into three types.

Highly pathogenic micro-organisms can cause infection in an individual with anormal defense capacity, e.g., Salmonella spp.

Potentially pathogenic micro-organisms can cause infection in a patient withimpaired defense mechanisms, e.g., S. pneumoniae in community practice andPseudomonas aeruginosa in hospital practice. These two types of microbescause both morbidity and mortality.

Microbes of low pathogenicity cause infection under special circumstances only,e.g., anaerobes can cause abscesses when tissue necrosis is present. Low levelpathogens in general only cause morbidity.

Intrinsic pathogenicity refers to the capacity to cause infection. The intrinsicpathogenicity index (IPI) is defined as the ratio of the number of patients whodevelop an infection due to a particular micro-organism and the number ofpatients who carry the organism in throat and/or rectum. Indigenous flora,including anaerobes and Streptococcus viridans, rarely cause infections despitebeing carried in high concentrations. The IPI is typically in the range 0.01-0.03.Coagulase-negative staphylococci and enterococci are also carried in theoropharynx in high concentrations, but are unable to cause lower airway infec-tions. High-level pathogens, such as Salmonella spp, have an IPI approaching 1in the gut. Potentially pathogenic micro-organisms have an IPI in the range 0.1-0.3. These include the “community” or “normal” microbes and the “hospital” or“abnormal” AGNBs, which are the targets of SDD.

Migration

Migration is the process whereby micro-organisms carried in the throat and gutmove to colonize and possibly infect internal organs. Migration is promoted byunderlying chronic disease, some drugs, and invasive devices.

Outbreak

An outbreak is defined as an event where two or more patients in a definedlocation are infected by identical micro-organisms, usually within an arbitrarytime period of 2 weeks. Such episodes often occur with multi-resistant micro-organisms such as Pseudomonas, MRSA, or vancomycin-resistant enterococci.In the pediatric ICU, viruses such as respiratory syncytial virus or rotavirus canalso be a major problem. Outbreak of carriage of microbes may have consider-able significance for infection control.



Overgrowth

Overgrowth is defined as the presence of a high concentration of potentiallypathogenic micro-organisms, ≥3+ or ≥105CFU/ml, in surveillance samples fromthe digestive tract [24]. Overgrowth in the small intestine can induce a state ofsystemic immunoparalysis. Overgrowth is also a risk factor for the colonizationand infection of internal organs, translocation into the blood stream, selectionof resistant micro-organisms, and transmission of organisms between patients.

Pneumonia

Microbiologically confirmed pneumonia1. Presence of new or progressive infiltrates on a chest X-ray for ≥48 h and2. Fever ≥38.3oC and3. Leukocytosis (WBC >12,000/ml) or leukopenia (WBC <4,000/ml) and4. Purulent tracheal aspirate containing ≥2+ WBC per high-power field and5. Tracheal aspirate specimen yielding ≥105 CFU/ml or6. Protected brush specimen (PBS) yielding >103 CFU/ml or7. Broncho-alveolar lavage (BAL) specimen yielding >104 CFU/ml

Clinical diagnosis only. This is when criteria 1-4 fulfilled, but tracheal aspirates,PBS, or BAL are sterile. Criteria for the diagnosis of pneumonias remain contro-versial [3]. The situation is sometimes complicated by viral etiologies and/orprior antibiotic treatment, particularly in infants and children. There is also over-lap with other pathophysiological terms, such as pneumonitis and bronchiolitis.

Resistance

A micro-organism is considered to be resistant to a particular antimicrobialagent if:1. The minimal inhibiting concentration of the antimicrobial agent against a

colonizing or infecting microbial species is higher than the non-toxic bloodconcentration after systemic administration.

2. The minimum bactericidal concentration of the antimicrobial agent againstmicrobes carried in throat and gut is higher than the non-toxic concentra-tion achieved by enteral administration.

Samples

Diagnostic. Diagnostic or clinical samples are taken from sites that are normal-ly sterile to diagnose infection or evaluate response to therapy. Samples aretaken on clinical indication only from blood, lower airways, CSF, urinary tract,wounds, peritoneum, joints, sinuses, or conjunctiva.



Surveillance. Surveillance samples are taken from the oropharynx and rectumon admission and subsequently at regular intervals (usually twice weekly).These specimens are needed to:1. Evaluate the carriage of potentially pathogenic micro-organisms2. Assess the eradication of potential pathogens by non-absorbable antimicro-

bial regimens used in SDD protocols3. Detect the carriage of resistant strains

Selective Decontamination of the Digestive Tract

The full SDD protocol has four components [23, 25]:1. A parenteral antibiotic is administered for the first few days to prevent or

control primary endogenous infection (e.g., cefotaxime)2. Non-absorbable antimicrobials are administered into the oropharynx and

gastrointestinal tract, when surveillance cultures show abnormal carriage.The usual combination is polymyxin E (colistin), tobramycin, and ampho-tericin B (PTA).

3. A high standard of hygiene is required to prevent exogenous infectionepisodes.

4. Regular surveillance samples of throat and rectum are obtained to diagnosecarrier states and monitor the efficacy of SDD.The policy at Alder Hey is to use SDD “à la carte”, guided by the abnormal

carrier state detected by surveillance samples. However, most ICUs that useSDD start the regimen on admission, irrespective of surveillance swab results.

Systemic Inflammatory Response Syndrome, Sepsis, Septic Shock

Definitions for systemic inflammatory response syndrome (SIRS), sepsis, severesepsis, and septic shock have been extensively reviewed in the last decade, par-ticularly in relation to the inclusion criteria for clinical trials [8, 26, 27].Consensus definitions form categories based on cut-off points in a number ofvariables. Cut-off points based on indices of perfusion can be difficult to evalu-ate in practice. Furthermore, a patient’s clinical state can change rapidly [28].Microbiological confirmation or exclusion of infection may occur a consider-able time after the clinical diagnosis of septic states. The cut-offs and thresh-olds have to be adjusted in the pediatric population [29].

Systemic inflammatory response syndrome is the systemic inflammatoryresponse to a wide variety of clinical insults [8, 30, 31], manifested by two ormore of the following1. Temperature >38 or <36oC2. Heart rate >90 beats per minute



3. Respiratory rate >20 breaths per minute4. White blood cell count >12,000/mm3 or <4,000mm3, or >10% immature forms

Sepsis is defined as SIRS with a clear infectious etiology.

Septicaemia is sepsis with a positive blood culture. In contrast, bacteraemia isdefined as a positive blood culture exhibiting no clinical symptoms.

Severe sepsis is defined as sepsis with organ dysfunction, hypoperfusion, orhypotension. Manifestations of hypoperfusion may include, but are not limitedto, lactic acidosis, oliguria, and acute alterations in mental state.

Septic shock is sepsis-induced hypotension, persisting despite adequate fluidresuscitation, together with manifestations of hypoperfusion. Hypotension isdefined as a systolic blood pressure <90 mmHg or a reduction of >40 mmHgfrom baseline in the absence of other causes of hypotension.

Sinusitis

Sinusitis is infection of the paranasal sinuses - maxillary, ethmoidal, frontal, orsphenoidal. Symptoms and signs such as localized tenderness and purulent dis-charge may be absent in the sedated ICU patient. Fever (temperature ≥38.3oC)and leukocytosis (WBC >12,000/mm3) or leukopenia (WBC <4,000/mm3) arethe main clinical features. Plain radiographs or CT imaging may show fluid lev-els of obliteration in the sinus air spaces. Surgical drainage is performed toobtain microbiological confirmation (≥3+ or ≥105 CFU/ml of pus, together with≥2+ leukocytes).

Tracheitis, bronchitis

In the absence of pulmonary infiltrates on the chest X-ray tracheitis/bronchitisis defined as:1. Purulent tracheal aspirate and2. Fever >38.3oC and3. Leukocytosis (WBC >12,000/mm3) or leukopenia (WBC <4,000/mm3)4. ≥105 CFU/ml of tracheal aspirate

Translocation (Transmural Migration)

Translocation is defined as the passage of viable micro-organisms from thethroat and gut through mucosal barriers to regional lymph nodes and internalorgans, including the blood.



Transmission

Transmission is defined as the spread of micro-organisms between patients, bymeans of “vectors” such as the hands of carers. Measures to control transmis-sion include isolation, hand washing, protective clothing, and care of equip-ment.

Urinary Tract Infection

Urinary tract infection is defined as infection of the urinary tract, most fre-quently the bladder. The common clinical features of dysuria, suprapubic pain,frequency, and urgency are often absent in the sedated ICU patient. The diag-nosis rests on a freshly voided catheter urine specimen or suprapubic samplecontaining ≥105 bacteria or yeasts/ml of urine and ≥5 WBC per high-powerfield.

Wound Infection

Wound infection is defined as purulent discharge from wounds, signs of localinflammation, and a culture yielding ≥3+ or ≥105 CFU/ml. The isolation of skinflora in the absence of these features is considered contamination.

References

1. Feinstein AR (1967) Clinical judgment. Williams and Wilkins, Baltimore2. Feinstein AR (1994) Clinical judgment revisited: the distraction of quantitative

models. Ann Intern Med 120:799-8053. Bonten M (1999) Controversies on diagnosis and prevention of ventilator-associated

pneumonia. Diagn Microbiol infect Dis 34:199-2044. Toltzis P, Rosolowski B, Salvator A (2001) Etiology of fever and opportunities for

reduction of antibiotic use in a pediatric intensive care unit. Infect Control HospEpidemiol 22:499-504

5. Bone RC (1991) Let’s agree on terminology: definitions of sepsis. Crit Care Med19:973-976

6. Canadian Multiple Organ Failure Study Group (1991) “Sepsis” – clarity of existing ter-minology…or more confusion? Crit Care Med 19:996-998

7. Bone RC, Grodzin CJ, Balk RA (1997) Sepsis: a new hypothesis for pathogenesis of thedisease process. Chest 112:235-243

8. Levy MM, Fink MP, Marshall JC et al (2003) 2001 SCCM/ESICM/ACCP/ATS/SISInternational Sepsis Definitions Conference. Crit Care Med 31:1250-1256

9. Rixen D, Siegel JH, Friedman HP (1996) “Sepsis/SIRS,” physiologic classification, seve-rity stratification, relation to cytokine elaboration and outcome prediction in post-trauma critical illness. J Trauma 41:581-598

10. Seeley AJE, Christou NV (2000) Multiple organ dysfunction syndrome: exploring the



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