Emerging Issues and Controversies in Infectious Disease

Emerging Issues and Controversies in Infectious Disease

Emerging Infectious Diseases of the 21st Century I.W. Fong Professor of Medicine, University of Toronto Infectious Diseases, St. Michael s Hospital For other titles in this series, go to: www.springer.com/series/5903 A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher.

I.W. Fong Editor Emerging Issues and Controversies in Infectious Disease

I.W. Fong Professor of Medicine University of Toronto St. Michael s Hospital 30 Bond Street Toronto ON M5B 1W8 Canada fongi@smh.toronto.on.ca ISBN 978-0-387-84840-2 e-isbn 978-0-387-84841-9 DOI: 10.1007/978-0-387-84841-9 Library of Congress Control Number: 2008941665 # Springer Science+Business Media, LLC 2009 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper. springer.com

This book is dedicated to my wife, Cheryl, and to our grandchildren, Miranda and Aiden. v

Preface The past decade has been highlighted by numerous advances in medical scientific knowledge, medical technology, and diagnostic techniques but there have been fewer dramatic changes or improvements in the management of medical conditions. This volume in the Emerging Infectious Disease of the 21st century series, addresses some of the emerging issues and controversies in Infectious Diseases. The author has chosen these topics for review based on questions and contentions raised by medical residents, internists, emergency physicians, clinical infectious disease specialists, and family physicians. Hopefully the volume will provide guidance and answers to frequently asked questions in infectious disease to the generalists, specialists, and trainees in these areas, thus, facilitating improved patient care, prudent, and cost-effective management and investigation of these disorders. This volume reviews the diagnosis and treatment of some common infections facing clinicians and family physicians such as sinusitis, otitis media, and pertussis. Recent studies and surveys have shown that these conditions are often overdiagnosed and treated unnecessarily with antibiotics. The approach and guidelines for diagnosis and management are reviewed in this volume. Other more complicated but less common conditions challenging internists, clinical infectious disease consultants, and other specialists are also reviewed (i.e., meningitis, ventilator associated pneumonia, sepsis, hepatitis C, B, etc.). This book discusses current guidelines provided by various medical societies for various infections, and analyzes the evidence to support those guidelines as well as contentious issues. vii

Contents Section A: Bacterial and Fungal Infections 1 Issues in Central Nervous System Infections... 3 1.1 Bacterial Meningitis... 3 1.1.1 Introduction... 3 1.1.2 Pathophysiology of Meningitis... 3 1.1.3 Clinical Issues in Meningitis... 4 1.2 Adjunctive Therapy in Tuberculous Meningitis... 15 1.2.1 Background... 15 1.2.2 Treatment of Tuberculous Meningitis... 17 1.3 Adjunctive Therapy in Fungal Meningitis... 18 1.3.1 Background... 18 1.4 Future Directions... 20 References... 22 2 Emerging Issues in Head and Neck Infections... 27 2.1 Current Issues in Sinusitis... 27 2.1.1 Background... 27 2.1.2 Pathophysiology of Sinusitis... 27 2.1.3 Issues in Diagnosis of Bacterial Sinusitis... 28 2.1.4 Microbiology of Sinusitis... 30 2.1.5 Treatment of Acute Bacterial Sinusitis... 32 2.1.6 Management of Chronic Sinusitis... 35 2.1.7 Issues in Acute Otitis Media... 36 2.1.8 Clinical Practice Guidelines... 40 2.1.9 Future Directions... 41 References... 43 Section B: Emerging Trends in Pulmonary Infection 3 Current Issues in Ventilator-Associated Pneumonia... 49 3.1 Background... 49 3.2 Issues in the Diagnosis of VAP... 49 3.2.1 Microbiological Techniques for Diagnosis...... 51 ix

x Contents 3.2.2 New Diagnostic Methods for VAP... 55 3.3 Microbial Etiology of VAP... 56 3.4 Issues in Treatment of VAP... 57 3.5 Prevention of VAP... 60 3.5.1 Antibiotic Prophylaxis for Prevention of VAP... 61 3.5.2 Maintaining Gastric Acidity to Prevent VAP.... 63 3.5.3 Methods to reduce Aspiration... 64 3.5.4 Ventilator Circuit and VAP... 65 3.5.5 Summary of Prevention... 65 3.6 Future Directions... 66 References... 67 4 Emerging Issues in Pulmonary Infections of Cystic Fibrosis... 75 4.1 Introduction...... 75 4.2 Pathobiology of Cystic Fibrosis... 75 4.3 Microbiology..... 78 4.3.1 Pseudomonas aeruginosa... 79 4.3.2 Late-Emerging Pathogens... 80 4.3.3 Stentotrophomonas and Alcaligenes Species.... 81 4.3.4 Mycobacteria Species... 81 4.3.5 Aspergillus Species and Other Fungi... 82 4.3.6 Viral Infections... 83 4.4 Management of Infections in CF... 83 4.4.1 Infants with CF... 84 4.4.2 Antipseudomonal Therapy... 84 4.4.3 Maintenance Therapy... 85 4.4.4 Treatment of Pulmonary Exacerbation... 87 4.4.5 Treatment of Other Emerging Pathogens... 89 4.5 Prevention of Infections in CF... 90 4.6 Adjunctive Therapy for Pulmonary Exacerbation... 90 4.6.1 Anti-inflammatory Therapy... 91 4.7 Future Directions... 92 References... 94 5 Re-Emergence of Childhood Respiratory Infections in Adults (RSV & Pertussis)... 103 A: Respiratory Syncytial Virus infection in Adults... 103 5.1 Introduction... 103 5.2 Microbiology and Pathogenesis... 103 5.2.1 Immunity... 104 5.2.2 Epidemiology... 105 5.2.3 Management in Adults... 107 5.2.4 Prevention... 108 5.2.5 Future Directions... 109 References... 109

Contents xi B: Pertussis in Adults... 113 5.3 Introduction... 113 5.3.1 Microbiology and Pathogenesis... 114 5.3.2 Immunity... 115 5.3.3 Epidemiology... 116 5.3.4 Diagnosis and Management... 118 5.3.5 Prevention... 119 5.3.6 Future Directions... 120 References... 121 Section C: New Concepts and Trends 6 New Concepts and Emerging Issues in Sepsis... 127 6.1 Introduction...... 127 6.2 Definitions... 128 6.3 Immune Response... 128 6.4 Pathogenesis...... 130 6.4.1 Hemodynamics... 132 6.4.2 Mechanisms... 133 6.4.3 Apoptosis of Immune Cells... 135 6.4.4 Immunoparalysis... 136 6.4.5 Tissue Oxygenation... 137 6.4.6 Coagulation... 138 6.4.7 Complement System... 139 6.4.8 ARDS in Sepsis... 140 6.5 Management in Sepsis... 141 6.6 Early Goal-Directed Therapy... 141 6.7 Antimicrobial Therapy in Severe Sepsis... 142 6.8 Activated Protein C... 144 6.9 Corticosteroids in Severe Sepsis... 145 6.10 Intensive Insulin Therapy... 146 6.11 Vasopressin and Vasopressors... 147 6.12 Blood Products in Sepsis... 147 6.13 Ventilation and Other Adjunctive Therapy... 148 6.14 Immunotherapies for Sepsis... 149 6.15 Genetics and Sepsis... 150 6.16 Future Directions... 151 6.17 Conclusion...... 154 References... 154 7 Febrile Neutropenia: Management Issues... 165 7.1 Introduction...... 165 7.2 Pathogenesis...... 166 7.3 Febrile Neutropenia Definition... 167 7.4 Microbiology and Etiology... 168

xii Contents 7.4.1 Initial Antibiotic Therapy... 169 7.4.2 High-Risk Patients... 171 7.4.3 Choice of Monotherapy... 173 7.5 Duration of Therapy... 174 7.6 Empiric Antifungal Therapy... 175 7.7 Prevention... 177 7.7.1 Prophylactic Antibiotics... 177 7.7.2 Colony-Stimulating Factors... 178 7.7.3 Antifungal Prophylaxis... 179 7.8 Future Directions... 180 References... 181 8 Emerging Issues and Trends in Clostridium difficile Colitis... 189 8.1 Introduction...... 189 8.2 Microbiology..... 189 8.3 Pathogenesis...... 190 8.3.1 Binary Toxin and New Hypervirulent Strains... 192 8.4 Clinical Aspects... 194 8.4.1 Antibiotic-Associated Diarrhea... 195 8.4.2 Risk Factors for CDAD... 197 8.5 Diagnosis... 199 8.6 Management...... 200 8.6.1 Specific Therapy... 201 8.6.2 Recurrences of CDAD... 204 8.6.3 Prevention... 209 8.6.4 Future Directions... 212 References... 214 9 Probiotics in Infectious Diseases... 227 9.1 Introduction...... 227 9.2 Background... 228 9.3 Mechanisms of Action... 229 9.3.1 Mucosal Integrity... 229 9.3.2 Colonization Resistance... 231 9.3.3 Inactivation of Microbial Toxins... 232 9.3.4 Immunomodulation... 232 9.3.5 Bacterial Translocation... 234 9.4 Clinical Application of Probiotics... 235 9.4.1 Probiotics for Newborns and Children... 235 9.4.2 Antibiotic-Associated Diarrhea... 238 9.4.3 Urogenital Infections... 240 9.4.4 Probiotics in Vaginitis... 245 9.4.5 Miscellaneous Infections... 246 9.5 Probiotics as Food Additives... 249 9.6 Adverse Effects of Probiotics... 250

Contents xiii 9.7 Conclusion and Future Directions... 250 References... 251 10 Device-Related Infections... 261 10.1 Introduction.... 261 10.2 Pathogenesis of Device-Related Infections... 263 10.2.1 Impairment of Local Defence... 264 10.2.2 Resistance to Antimicrobial Agents... 265 10.3 Specific Device-Related Infections... 267 10.3.1 Intravascular Devices... 267 10.3.2 Prevention of Central versus Catheter Infections... 274 10.4 Cardiovascular Device Infectious... 277 10.4.1 Cardiac Devices and Infections... 277 10.4.2 Trends in Prosthetic Valve Endocarditis.... 277 10.4.3 Infections of ICD, LVAD and Pacemakers... 280 10.5 Vascular Grafts... 285 10.6 Future Directions... 287 References... 288 11 Current Concepts of Orthopedic Implants and Prosthetic Joint Infections... 299 11.1 Introduction.... 299 11.2 Microbiological Aspects... 299 11.3 Diagnosis... 302 11.4 Clinical Presentation... 304 11.5 Management... 305 11.5.1 Basis of Medical Therapy... 305 11.5.2 Principles of Surgical Management... 308 11.5.3 Treatment Algorithm... 312 11.5.4 Issues with Antimicrobial Therapy... 313 11.6 Prevention of Orthopedic Device Infections... 316 11.7 Future Directions... 318 11.8 Conclusion..... 319 References... 319 12 Combination Antimicrobial Therapies... 327 12.1 Introduction.... 327 12.2 Bacterial Infections... 328 12.2.1 Bacterial Infective Endocarditis... 328 12.2.2 In Vitro Testing of Synergy... 329 12.2.3 Animal Models of Infective Endocarditis... 330 12.2.4 Clinical Trials in Bacterial Endocarditis.... 332 12.2.5 Gram-Negative Bacilli Infections... 337 12.2.6 Community-Acquired Pneumonia... 338

xiv Contents 12.3 Fungal Infections and Combination Therapy... 338 12.3.1 In Vitro Antifungal Combination Assays... 339 12.3.2 Antifungal Combinations for Candida species... 342 12.3.3 Combination Therapy for Cryptococcal Meningitis... 344 12.3.4 Combination Therapy for Invasive Aspergillosis... 345 12.4 Viral Infections... 347 12.4.1 Chronic Hepatitis C Infections... 347 12.4.2 Chronic Hepatitis B Virus... 351 12.5 Parasitic Infections... 355 12.5.1 Antimalarial Combination Therapies... 355 12.5.2 Filariasis Therapies... 358 12.5.3 Leishmaniasis... 360 12.5.4 African Trypanosomiasis (Sleeping Sickness)... 361 12.6 Conclusion..... 362 12.7 Future Directions... 364 References... 364 Index... 379

Acknowledgment I am very grateful to Winnie Yau for her secretarial and administrative assistance and to Maria Isabel Suarez, Bogusia Skucinska, and my wife (Cheryl) for their stenographic assistance in the preparation of this manuscript. I am also indebted to Carolyn Ziegler for her invaluable assistance in performing literature searches. xv