Infectious Diseases in Critical Care Medicine Third Edition pdf

Infectious
Diseases in
Critical Care
Medicine
Cunha_978-1420092400_TP.indd 1 10/5/09 4:21:18 PM
INFECTIOUS DISEASE AND THERAPY
Series Editor
Burke A. Cunha
Winthrop-University Hospital
Mineola, New York
and
State University of New York School of Medicine
Stony Brook, New York
1. Parasitic Infections in the Compromised Host, edited by Peter D. Walter and Robert
M. Genta
2. Nucleic Acid and Monoclonal Antibody Probes: Applications in Diagnostic Method-
ology, edited by Bala Swaminathan and Gyan Prakash
3. Opportunistic Infections in Patient s with the Acquired Immuno deficiency Syndrome,
edited by Gifford Leoung and John Mills
4. Acyclovir Therapy for Herpesvirus Infections, edited by David A. Baker
5. The New Generation of Quinolones, edited by Clifford Siporin, Carl L. Heifetz, and
John M. Domagala
6. Methicillin-Resistant Staphylococcus aureus: Clinical Management and Laboratory
Aspects, edited by Mary T. Cafferkey
7. Hepatitis B Vaccines in Clinical Practice, edited by Ronald W. Ellis
8. The New Macrolides, Azalides, and Streptogramins: Pharmacology and Clinical
Applications, edited by Harold C. Neu, Lowell S. Young, and Stephen H. Zinner
9. Antimicrobial Therapy in the Elderly Patient, edited by Thomas T. Yoshikawa and
Dean C. Norman
10. Viral Infections of the Gastrointestinal Tract: Second Edition, Revised and Expanded,

edited by Albert Z. Kapikian
11. Development and Clinical Uses of Haemophilus b Conjugate Vaccines, edited by
Ronald W. Ellis and Dan M. Cranoff
12. Pseudomonas aeruginosa Infections and Treatment, edited by Aldona L. Battch and
Raymond P. Smith
13. Herpesvirus Infections, edited by Ronald Glaser and James F. Jones
14. Chronic Fatigue Syndrome, edited by Stephen E. Straus
15. Immunotherapy of Infections, edited by K. Noel Masihi
16. Diagnosis and Management of Bone Infections, edited by Luis E. Jauregui
17. Drug Transport in Antimicrobial and Anticancer Chemotherapy, edited by Nafsika H.
Georgopapadakou
18. New Macrolides, Azalides, and Streptogramins in Clinical Practice, edited by Harold
C. Neu, Lowell S. Young, Stephen H. Zinner, and Jacques F. Acar
19. Novel Therapeutic Strategies in the Treatment of Sepsis, edited by David C.
Morrison and John L. Ryan
20. Catheter-Related Infections, edited by Harald Seifert, Bernd Jansen, and Barry M.
Farr
21. Expanding Indications for the New Macrolides, Azalides, and Streptogramins, edited
try Stephen H. Zinner, Lowell S. Young, Jacques F. Acar, and Harold C. Neu
22. Infectious Diseases in Critical Care Medicine, edited by Burke A. Cunha
23. New Considerations for Macrolides, Azalides, Streptogramins, and Ketolides, edited
by Stephen H. Zinner, Lowell S. Young, Jacques F. Acar, and Carmen Ortiz-Neu
24. Tickborne Infectious Dise ases: Diagnosis and Management, edited by Burke A.
Cunha
25. Protease Inhibitors in AIDS Therapy, edited by Richard C. Ogden and Charles W.
Flexner
26. Laboratory Diagnosis of Bacterial Infections, edited by Nevio Cimolai
27. Chemokine Receptors and AIDS, edited by Thomas R. O’Brien
28. Antimicrobial Pharmacodynamics in Theory and Clinical Practice, edited by Charles
H. Nightingale, Takeo Murakawa, and Paul G. Ambrose

29. Pediatric Anaerobic Infections: Diagnosis and Management, Third Edition, Revised
and Expanded, Itzhak Brook
30. Viral Infections and Treatment, edited by Helga Ruebsamen-Waigmann, Karl Deres,
Guy Hewlett, and Reinhotd Welker
31. Community-Aquired Respiratory Infections, edited by Char les H. Nightingale, Paul
G. Ambrose, and Thomas M. File
32. Catheter-Related Infections: Second Edition, edited by Harald Seifert, Bernd Jansen,
and Barry Farr
33. Antibiotic Optimization: Concepts and Strategies in Clinical Practice (PBK), edited by
Robert C. Owens, Jr., Charles H. Nightingale, and Paul G. Ambrose
34. Fungal Infections in the Immunocompromised Patient, edited by John R. Wingard
and Elias J. Anaissie
35. Sinusitis: From Microbiology To Management, edited by Itzhak Brook
36. Herpes Simplex Viruses , edited by Marie Studahl, Paola Cinque and Toms
Bergstro
¨
m
37. Antiviral Agents, Vaccines, and Immunotherapies, Stephen K. Tyring
38. Epstein-Barr Virus, edit ed by Alex Tselis and Hal B. Jenson
39. Infection Management for Geriatrics in Long-Term Care Facilities, Second Edition,
edited by Thomas T. Yoshikawa and Joseph G. Ouslander
40. Infectious Diseases in Critical Care Medicine, Second Edition, edited by Burke A.
Cunha
41. Infective Endocarditis: Management in the Era of Intravascular Devices, edited by
John L. Brusch
42. Fever of Unknown Origin, edited by Burke A. Cunha
43. Rickettsial Diseases, edited by Didier Raoult and Philippe Parola
44. Antimicrobial Pharmacodynamics in Theory and Clinical Practice, Second Edition,
edited by Charles H. Nightingale, Paul G. Ambrose, George L. Drusano, and Takeo
Murakawa

45. Clinical Handbook of Pediatric Infectious Disease, Third Edition, Russell W. Steele
46. Anaerobic Infections: Diagnosis and Management, Itzhak Brook
47. Diagnosis of Fungal Infections, edited by Johan A. Maertens and Kieren A. Marr
48. Antimicrobial Resistance: Problem Pathogens and Clinical Countermeasures, edited
by Robert C. Owens, Jr. and Ebbing Lautenbach
49. Lyme Borreliosis in Europe and North America, edited by, Sunil Sood
50. Laboratory Diagnosis of Viral Infections, Fourth Edition, edited by Keith R. Jerome
51. Infectious Diseases in Critical Care Medicine, Third Edition, edited by Burke A.
Cunha

Edited by
Burke A. Cunha
Winthrop-University Hospital
Mineola, New York, USA
State University of New York School of Medicine
Stony Brook, New York, USA
Infectious
Diseases in
Critical Care
Medicine
Third Edition
Cunha_978-1420092400_TP.indd 2 10/5/09 4:21:18 PM
Informa Healthcare USA, Inc.
52 Vanderbilt Avenue
New York, NY 10017
# 2010 by Informa Healthcare USA, Inc.
Informa Healthcare is an Informa business
No claim to original U.S. Government works
Printed in the United States of America on acid-free paper
10987654321

International Standard Book Number-10: 1-4200-9240-5 (hardcover : alk. paper)
International Standard Book Number-13: 978-1-4200-9240-0 (hardcover : alk. paper)
This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with
permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish
reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials
or for the consequence of their use.
No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or
other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information
storage or retrieval system, without written permission from the publishers.
For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://
www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923,
978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For
organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for
identification and explanation without intent to infringe.
Library of Congress Cataloging-in-Publication Data
Infectious diseases in cri tical care medicine / e dited by Burke A.
Cunha. – 3rd ed.
p. ; cm. — (Infectious disease and therapy ; 51)
Includes bibliographical references and index.
ISBN-13: 978-1-4200-9240-0 (hardcover : alk. paper)
ISBN-10: 1-4200-9240-5 (hardcover : alk. paper) 1. Nosocomial
infections. 2. Critical care medicine. 3. Intensive care units.
I. Cunha, Burke A. II. Series: Infectious disease and therapy ; 51.
[DNLM: 1. Communicable Diseases—diagnosis. 2. Communicable
Diseases—therapy. 3. Critical Care. 4. Diagnosis, Differential. 5.
Intensive Care Units. W1 IN406HMN v.51 2009 / WC 100 I4165 2009]
RC112.I4595 2009
616.9
0

0475—dc22
2009022304
For Corporate Sales and Reprint Permissions call 212-520-2700 or write to: Sales Department, 52 Vanderbilt Avenue,
7th floor, New York, NY 10017.
Visit the Informa Web site at
www.informa.com
and the Informa Healthcare Web site at
www.informahealthcare.com
for
Marie
Peerless wife and mother,
Provider of domestic peace and tranquility,
Paragon of truth and beauty,
Paradigm of earthly perfection . . .
With gratitude for her love and constant support.

Foreword
In the United States during the 1950s, the development of mechanical ventilation led to the
organization of special units in hospitals, where health care personnel with specific expertise
could efficiently focus on patients with highly technical or complex needs. Over the ensuing
years the sickest patients as well as those needing mechanical ventilation were grouped into
special care units. In 1958, Baltimore City Hospital developed the first multidisciplinary
intensive care unit. The concept of physician coverage 24 hours a day, seven days a week
became a logical approach to providing optimal care to the sickest, most complex patients.
Now, 50 years after the first multidisciplinary intensive care unit was opened, there are
now 5000 to 6000 intensive care units in the United States: Over 4000 hospitals offer one or
more critical care units, and there are 87,000 intensive care unit beds. Critical care represents
13.3% of hospital costs, totaling over $55 billion per year.
Health care providers are well aware of the role that infections play in the intensive care
unit. A substantial number of patients are admitted to the intensive care unit because of an

infection such as pneumonia, meningitis, or sepsis. A substantial number of patients admitted
to intensive care units for noninfectious disorders develop infections during their stay. Thus,
intensivists need expertise in the diagnosis, treatment, and prevention of infectious diseases.
Management of infections is pivotal to successful outcomes.
In this third edition of Infectious Diseases in Critical Care Medicine, Burke Cunha has
organized 31 chapters into an exceedingly practical and useful overview. Providers often find
it surprisingly difficult to distinguish infectious and noninfectious syndromes, especially when
patients have life-threatening processes that evoke similar systemic inflammatory responses.
Part I and Part II provide many clinical pearls that help with diagnosis and with developing a
strategy for initial patient management. Specific chapters focus on special intensive care unit
problems, such as central venous catheter infections, nosocomial pneumonias, endocarditis,
and Clostridium difficile infection. Particularly useful are chapters on special populations that
many clinicians rarely encounter: tropical diseases, cirrhosis, burns, transplants, or tubercu-
losis. Chapters on therapy also provide practical advice focused on critically ill patients, in
whom choice of agent, toxicities, drug interactions, and pharmacokinetics may be substantially
different from patients who are less seriously ill.
Critical care medicine is becoming more and more technology based. Genomics and
proteomics can predict susceptibility to various diseases and drug metabolic problems.
Patients can be assessed by ultrasonography to supplement physical examination. Diagnostic
biopsies can be performed on virtually any organ. Invasive arterial and venous monitoring as
well as monitoring of central nervous system and cardiac activity is commonplace.
Despite these advances in technology, knowledge of differential diagnosis, natural history,
and therapeutic options is still essential. To understand th ese processes, Burke Cunha has
assembled an impressive team of experienced clinicians to provide insight into the infectious
challenges of critical care medicine. This edition continues to provide relevant, current information
that will enhance clinical practice with this growing segment of hospitalized patients.
Henry Masur
Department of Critical Care Medicine
Clinical Center
National Institutes of Health

Bethesda, Maryland, U.S.A.
Preface to the First Edition
Infectious diseases are very important in critical care. In the critical care unit, infectious
diseases are seen in the differential diagnoses of the majority of patients, and maybe patients
acquire infections in the critical care unit. However, infectious disease is accorded a relatively
minor place in most critical care textbooks and does not receive the emphasis it deserves given
its presence in the critical care unit.
The infectious diseases encountered in the critical care setting are some of the most
severe and often difficult to diagnose. This book was developed for critical care practitioners,
the majority of whom are not trained in infectious diseases. It is written by clinicians in
infectious diseases in critical care and is meant as a handbook to provide valuable information
not included in critical care textbooks.
The text is unique in its emphasis and organization. It comprises four main sections: The
first section deals with general concepts of infectious diseases in the critical care unit; the
second deals with infectious diseases on the basis of clinical syndromes; the third deals with
specific infectious disease problems; and the fourth, with therapeutic considerations in critical
care patients.
One of the unique features of this book is its emphasis on differential diagnosis rather
than therapy. The main problem in the critical care unit is not therapeutic but diagnostic. If the
patient’s problem can be clearly delineated diagnostically, treatment is a relatively straight-
forward matter. Therapy cannot be appropriate unless related to the correct diagnosis.
Infectious Diseases in Critical Care Medicine emphasizes the importance of differential diagnoses
in each chapter and includes chapters on various “mimics” of infectious diseases. In fact, it is
with the “mimics” of various infectious disorders that the clinician often faces the most
difficult diagnostic challenges. This book should help the critical care unit clinician readily
discern between infectious diseases and the noninfectious disorders that mimic infection.
This is the first and only book that deals solely with infectious diseases in critical care
medicine. It is not meant to be a comprehensive textbook of infectious diseases. Rather, it
focuses on the most common infections likely to present diagnostic or therapeutic difficulties
in the critical care setting. The authors have approached their subjects from a clinical

perspective and have written in a style useful to clinicians. In addition to its usefulness to
critical care intensivists, this book should also be helpful to internists and infectious disease
clinicians participating in the care of patients in the critical care unit.
Burke A. Cunha
Preface to the Second Edition
Infectious diseases continue to represent a major diagnostic and therapeutic challenge in the
critical care unit. Infectious diseases maintain their preeminence in the critical care unit setting
because of their frequency and importance in the critical unit patient population.
Since the first edition of Infectious Diseases in Critical Care Medicine, there have been newly
described infectious diseases to be considered in differential diagnosis, and new antimicrobial
agents have been added to the therapeutic armamentarium.
The second edition of Infectious Diseases in Critical Care Medicine continues the clinical
orientation of the first edition. Differential diagnostic considerations in infectious diseases
continue to be the central focus of the second edition.
Clinicians caring for acutely ill patients in the CCU are confronted with the common
problem of differentiating noninfectious disease mimics from their infectious disease
counterparts. For this reason, the differential diagnosis of noninfectious diseases remain an
important component of infectious diseases in the second edition. The second edition of
Infectious Diseases in Critical Care Medicine emphasizes differential clinical features that enable
clinicians to sort out complicated diagnostic problems.
Because critical care unit patients often have complicated/interrelated multisystem
disorders, subspecialty expertise is essential for optimal patient care. Early utilization of
infectious disease consultation is important to assure proper application/interpretation of
appropriate laboratory tests and for the selection/optimization of antimicrobial therapy.
Selecting the optimal antimicrobial for use in the CCU is vital. As important is the optimization
of antimicrobial dosing to take into account the antibiotic’s pharmacokinetic and pharmaco-
dynamic attributes. The infectious disease clinician, in add ition to optimizing dosing
considerations is also able to evaluate potential antimicrobial side effects as well as drug–
drug interactions, which may affect therapy. Infectious disease consultations can be helpful in
differentiating colonization ordinarily not treated from infection that should be treated.

Physicians who are not infectious disease clinicians lack the necessary sophistication in clinical
infectious disease training, medical microbiology, pharmacokinetics/pharmacodynamics, and
diagnostic experience. Physicians in critical care units should rely on infectious disease
clinicians as well as other consultants to optimize care these acutely ill patients.
The second edition of Infectious Diseases in Critical Care Medicine has been streamlined,
maintaining the clinical focus in a more compact volume. Again, the authors have been
selected for their expertise and experience. The contributors to the book are world-class
teacher/clinicians who have in their writings imparted wisdom accrued from years of clinical
experience for the benefit of the critical care unit physician and their patients. The second
edition of Infectious Diseases in Critical Care Medicine remains the only book dealing with
infections in critical care.
Burke A. Cunha
Preface to the Third Edition
Infectious disease aspects of critical care have changed much since the first edition was
published in 1998. Infectious diseases are ever present and are becoming important in critical
care. Infectious Diseases in Critical Care Medicine (third edition) remains the only book
exclusively dedicated to infectious diseases in critical care.
Importantly, Infectious Diseases in Critical Care Medicine (third edition) is written from the
infectious disease perspective by clinicians for clinicians who deal with infectious diseases in
critical care. The infectious disease perspective is vital in the clinical diagnostic approach to
noninfectious and infectious disease problems encountered in critical care. The third edition of
this book is not only completely updated but includes new topics that have become important
in infectious diseases in critical care since the publication of the second edition.
The hallmark of clinical excellence in infectious disease consultation is the diagnostic
experience and expertise of the infectious disease consultant. The clinical approach should not
be to arrive at a diagnosis by ordering a bewildering number of clinically irrelevant tests
hoping for clues from abnormal findings. The optimal differential diagnostic approach
depends on the infectious disease consultant carefully analyzing the history, physical findings,
and pertinent nonspecific laboratory tests in critically ill patients to focus diagnostic efforts.
Before a definitive diagnosis is made, the infectious disease consultant’s role as diagnostician is

to correctly interpret and correlate nonspecific laboratory tests in the correct clinical context,
which should prompt specific laboratory testing to rule in or rule out the most likely diagnostic
possibilities. As subspecialist consultants, infectious disease clinicians are excellent diagnos-
ticians. For this reason, infectious disease consultation is of vital importance for all but the
most straightforward infectious disease problems encountered in critical care.
Another distinguishing characteristic of infectious disease clinicians is that they are both
diagnostically and therapeutically focused. Many noninfectious disease clinicians often tend to
empirically “cover” patients with an excessive number of antibiotics to provide coverage
against a wide range of unlikely pathogens. Currently, most of resistance problems in critical
care units result from not appreciating the resistance potential of some commonly used
antibiotics in many multidrug regimens, such as ciprofloxaxin, imipenem, and ceftazidime.
Some contend this approach is defensible because with antibiotic “deescalation” the
unnecessary antibiotics can be discontinued subsequently. Unfortunately, except for culture
results from blood isolates cultures with skin/soft tissue infections, or cerebrospinal fluid with
meningitis, usually there are no subsequent microbiologic data upon which to base antibiotic
deescalation, such as nosocomial pneumonia, abscesses, and intra-abdominal/pelvic infec-
tions. The preferred infectious disease approach is to base initial empiric therapy or covering
the most likely pathogens rather than clinically unlikely pathogens. Should diagnostically
valid data become available, a change in antimicrobial therapy may or may not be warranted
on the basis of new information.
Because infectious disease consultation is so important in the differential diagnostic
approach in critical care, this book’s emphasis is on differential diagnosis. If the diagnosis is
inaccurate/incorrect, empiric therapy will necessarily be incorrect. To assist those taking care
of critically ill patients, chapters on physical exam clues and their mimics, ophthalmologic
clues and their mimics in infectious disease, and radiologic clues and their mimics in infectious
disease have been included in this edition. In addition, several chapters notably, “Clinical
Approach to Fever’’ and ‘‘Fever and Rash,” also emphasize on physical findings.
Since the last edition, some infectious diseases, such as Clostridium difficile diarrhea/
colitis, SARS (severe acute respiratory syndrome), HPS (hantavirus pulmonary syndrome),
avian influenza (H5N1), and swine influenza (H1N1) have become important in critical care

medicine.
Another important topic has been added on infections related to immunomodulating/
immunosuppressive agents. The widespread introduction of immune modulation therapy has
resulted in a recrudescence of many infections due to intracellular pathogens, which are
important to recognize in patients receiving these agents. Because miliary tuberculosis is so
important and is not an infrequent complication of steroid/immunosuppressive therapy, a
chapter on this topic also has been included in the third edition.
As mentioned, antibiotic resistance in the critical care unit is a continuing problem with
short- and long-term clinical consequences. Currently, methicillin-resistant Staphylococcos
aureus and vancomycin-resistant enterococci are the most important gram-positive pathogens
in critical care, and a chapter has been added on antibiotic therapy of these pathogens. Among
the multidrug-resistant aerobic gram-negative bacilli, Klebsiella pneumoniae, Pseudomonas
aeruginosa, and Acinetobacter baumannii continue to be difficult therapeutic problems, and a
chapter has been included on this important topic.
The contributors to the third edition of Infectious Diseases in Critical Care Medicine are
nationally or internationally acknowledged experts in their respective fields. The authors have
been selected for their clinical excellence and experience. They are teacher-clinicians also
known for their ability to effectively distill the key points related to their topics.
The third edition is not just a compendium of current guidelines. Guidelines are not
definitive and for this reason often change over time. Guideline followers may not agree with
this book’s clinical approach which is evidence based, but tempered by clinical experience.
Especially in critical care, the key determinant of optimal patient care is experienced based
clinical judgment which the clinician contributors have provided.
In summary, the this edition is both up-to-date and better than ever. Now in its third
edition, Infectious Diseases in Critical Care Medicine, written by clinicians for clinicians, remains
the only major text exclusivel y dealing with the major infectious disease syndromes
encountered in critical care medicine.
Burke A. Cunha
Preface to the Third Edition xiii
Contents

Foreword Henry Masur ix
Preface to the First Edition x
Preface to the Second Edition xi
Preface to the Third Edition xii
Contributors xvii
PART I: DIAGNOSTIC APPROACH IN CRITICAL CARE
1. Clinical Approach to Fever in Critical Care 1
Burke A. Cunha
2. Fever and Rash in Critical Care 19
Lee S. Engel, Charles V. Sanders, and Fred A. Lopez
3. Physical Exam Clues to Infectious Diseases and Their Mimics in Critical Care 49
Yehia Y. Mishriki
4. Ophthalmologic Clues to Infectious Diseases and Their Mimics in Critical Care 66
Cheston B. Cunha, Michael J. Wilkinson, and David A. Quillen
5. Radiology of Infectious Diseases and Their Mimics in Critical Care 76
Jocelyn A. Luongo, Orlando A. Ortiz, and Douglas S. Katz
6. Methicillin-Resistant Staphylococcus aureus/
Vancomycin-Resistant Enterococci Colonization
and Infection in the Critical Care Unit 102
C. Glen Mayhall
PART II: CLINICAL SYNDROMES IN CRITICAL CARE
7. Clinical Approach to Sepsis and Its Mimics in Critical Care 128
Burke A. Cunha
8. Meningitis and Its Mimics in Critical Care 134
Burke A. Cunha and Leon Smith
9. Encephalitis and Its Mimics in Critical Care 153
John J. Halperin
10. Severe Community-Acquired Pneumonia in Critical Care 164
Burke A. Cunha
11. Nosocomial Pneumonia in Critical Care 178

Emilio Bouza and Almudena Burillo
12. Intravenous Central Line Infections in Critical Care 208
Burke A. Cunha
13. Infective Endocarditis and Its Mimics in Critical Care 218
John L. Brusch
14. Intra-abdominal Surgical Infections and Their Mimics in Critical Care 260
Samuel E. Wilson
15. Clostridium difficile Infection in Critical Care 271
Karin I. Hjalmarson and Sherwood L. Gorbach
16. Urosepsis in Critical Care 288
Burke A. Cunha
17. Severe Skin and Soft Tissue Infections in Critical Care 295
Mamta Sharma and Louis D. Saravolatz
PART III: DIFFICULT DIAGNOSTIC PROBLEMS IN CRITICAL CARE
18. Tropical Infections in Critical Care 322
MAJ Robert Wood-Morris, LTC Michael Zapor, David R. Tribble, and Kenneth F. Wagner
19. Infections in Cirrhosis in Critical Care 341
Laurel C. Preheim
20. Severe Infections in Asplenic Patients in Critical Care 350
Mohammed S. Ahmed and Nancy Khardori
21. Infections in Burns in Critical Care 359
Steven E. Wolf, Basil A. Pruitt, Jr., and Seung H. Kim
22. Infections Related to Steroids in Immunosuppressive/Immunomodulating
Agents in Critical Care 376
Lesley Ann Saketkoo and Luis R. Espinoza
23. Infections in Organ Transplants in Critical Care 387
Patricia Mun
˜
oz, Almudena Burillo, and Emilio Bouza
24. Miliary Tuberculosis in Critical Care 420

Helmut Albrecht
25. Bioterrorism Infections in Critical Care 432
Dennis J. Cleri, Anthony J. Ricketti, and John R. Vernaleo
PART IV: ANTIMICROBIAL THERAPY
26. Selection of Antibiotics in Critical Care 487
Divya Ahuja, Benjamin B. Britt, and Charles S. Bryan
Contents xv
27. Antimicrobial Therapy of VRE and MRSA in Critical Care 497
Burke A. Cunha
28. Antibiotic Therapy of Multidrug-Resistant Pseudomonas aeruginosa,
Klebsiella pneumoniae, and Acinetobacter baumannii in Critical Care 512
Burke A. Cunha
29. Antibiotic Kinetics in the Febrile Multiple-System Trauma Patient
in Critical Care 521
Donald E. Fry
30. Antibiotic Therapy in the Penicillin Allergic Patient in Critical Care 536
Burke A. Cunha
31. Adverse Reactions to Antibiotics in Critical Care 542
Eric V. Granowitz and Richard B. Brown
Index 557
xvi Contents
Contributors
Mohammed S. Ahmed Infectious Diseases Fellow, Southern Illinois University School of
Medicine, Springfield, Illinois, U.S.A.
Divya Ahuja Department of Medicine, University of South Carolina School of Medicine,
Columbia, South Carolina, U.S.A.
Helmut Albrecht Division of Infectious Diseases, University of South Carolina, Columbia, South
Carolina, U.S.A.
Emilio Bouza Clinical Microbiology and Infectious Diseases Department, Hospital General
Universitario ‘‘Gregorio Maran

˜
o
´
n’’, Madrid, and CIBER de Enfarmedades Respiratorias (CIBERES),
Madrid, Spain
Benjamin B. Britt Providence Hospitals, Columbia, South Carolina, U.S.A.
Richard B. Brown Infectious Disease Division, Baystate Medical Center, Tufts University School of
Medicine, Springfield, Massachusetts, U.S.A.
John L. Brusch Department of Medicine, Harvard Medical School, Cambridge, Massachusetts,
U.S.A.
Charles S. Bryan Providence Hospitals, Columbia, South Carolina, U.S.A.
Almudena Burillo Clinical Microbiology Department, Hospital Universitario de Mo
´
stoles,
Madrid, Spain
Dennis J. Cleri Department of Medicine, Internal Medicine Residency Program, St. Francis
Medical Center, Trenton, and Seton Hall University School of Graduate Medical Education, South
Orange, New Jersey, U.S.A.
Burke A. Cunha Infectious Disease Division, Winthrop-University Hospital, Mineola, New York,
and State University of New York School of Medicine, Stony Brook, New York, U.S.A.
Cheston B. Cunha Department of Medicine, Brown University, Alpert School of Medicine,
Providence, Rhode Island, U.S.A.
Lee S. Engel Department of Medicine, Louisiana State University Health Sciences Center,
New Orleans, Louisiana, U.S.A.
Luis R. Espinoza Section of Rheumatology, Department of Medicine, Louisiana State University
Health Sciences Center, New Orleans, Louisiana, U.S.A.
Donald E. Fry Northwestern University Feinberg School of Medicine, Chicago, Illinois and
Department of Surgery, University of New Mexico School of Medicine, Albuquerque, New Mexico,
U.S.A.
Sherwood L. Gorbach Nutrition/Infection Unit, Department of Public Health and Family

Medicine, Tufts University School of Medicine, and Division of Geographic Medicine and Infectious
Diseases, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, U.S.A.
Eric V. Granowitz Infectious Disease Division, Baystate Medical Center, Tufts University School
of Medicine, Springfield, Massachusetts, U.S.A.
John J. Halperin Mount Sinai School of Medicine, Atlantic Neuroscience Institute, Overlook
Hospital, Summit, New Jersey, U.S.A.
Karin I. Hjalmarson Division of Geographic Medicine and Infectious Diseases, Department of
Medicine, Tufts Medical Center, Boston, Massachusetts, U.S.A.
Douglas S. Katz De partment of Radiology, Winthrop-U niversity Hospital, Mineola, New York,
U.S.A.
Nancy Khardori Department of Internal Medicine, Southern Illinois University School of
Medicine, Springfield, Illinois, U.S.A.
Seung H. Kim Burn Center, United States Army Institute of Surgical Research, San Antonio,
Texas, U.S.A.
Fred A. Lopez Department of Medicine, Louisiana State University Health Sciences Center, New
Orleans, Louisiana, U.S.A.
Jocelyn A. Luongo Department of Radiology, Winthrop-University Hospital, Mineola, New York,
U.S.A.
C. Glen Mayhall Division of Infectious Diseases and Department of Healthcare Epidemiology,
University of Texas Medical Branch at Galveston, Galveston, Texas, U.S.A.
Yehia Y. Mishriki Department of Medicine, Lehigh Valley Hospital Network, Allentown,
Pennsylvania, U.S.A.
Patricia Mun˜oz Clinical Microbiology and Infectious Diseases Department, Hospital General
Universitario, “Gregorio Maran
˜
o
´
n”, Madrid, Spain
Orlando A. Ortiz Department of Radiology, Winthrop-University Hospital, Mineola, New York,
U.S.A.

Laurel C. Preheim Departments of Medicine, Medical Microbiology and Immunology, Creighton
University School of Medicine, University of Nebraska College of Medicine, and V.A. Medical
Center, Omaha, Nebraska, U.S.A.
Basil A. Pruitt, Jr. Division of Trauma and Emergency Surgery, Department of Surgery,
University of Texas Health Science Center, San Antonio, and Burn Center, United States Army
Institute of Surgical Research, San Antonio, Texas, U.S.A.
David A. Quillen Department of Ophthalmology, George and Barbara Blankenship, Pennsylvania
State University, College of Medicine, Hershey, Pennsylvania, U.S.A.
xviii Contributors
Anthony J. Ricketti Section of Allergy and Immunology, Department of Medicine, and Internal
Medicine Residency, St. Francis Medical Center, Trenton, and Seton Hall University School of
Graduate Medical Education, South Orange, New Jersey, U.S.A.
Lesley Ann Saketkoo Section of Rheumatology, Department of Medicine, Louisiana State
University Health Sciences Center, New Orleans, Louisiana, U.S.A.
Charles V. Sanders Department of Medicine, Louisiana State University Health Sciences Center,
New Orleans, Louisiana, U.S.A.
Louis D. Saravolatz Division of Infectious Disease, Department of Internal Medicine, St. John
Hospital and Medical Center, and Wayne State University School of Medicine, Detroit, Michigan, U.S.A.
Mamta Sharma Division of Infectious Disease, Department of Internal Medicine, St. John Hospital
and Medical Center, and Wayne State University School of Medicine, Detroit, Michigan,
U.S.A.
Leon Smith Department of Medicine, St. Michael’s Medical Center, Newark, New Jersey, U.S.A.
David R. Tribble Enteric Diseases Department, Infectious Diseases Directorate, Naval Medical
Research Institute, Silver Spring, Maryland, U.S.A.
John R. Vernaleo Division of Infectious Diseases, Wyckoff Heights Medical Center, Brooklyn,
New York, U.S.A.
Kenneth F. Wagner Infectious Diseases and Tropical Medicine, Islamorada, Florida, U.S.A.
Michael J. Wilkinson Department of Ophthalmology, Pennsylvania State University, College of
Medicine, Hershey, Pennsylvania, U.S.A.
Samuel E. Wilson Department of Surgery, University of California, Irvine School of Medicine,

Orange, California, U.S.A.
Steven E. Wolf Division of Trauma and Emergency Surgery, Department of Surgery, University of
Texas Health Science Center, San Antonio, and Burn Center, United States Army Institute of
Surgical Research, San Antonio, Texas, U.S.A.
MAJ Robert Wood-Morris Infectious Diseases, B.C. Internal Medicine, Walter Reed Army
Medical Center, Washington, D.C., U.S.A.
LTC Michael Zapor Infectious Diseases Service, Walter Reed Army Medical Center, Washington,
DC, U.S.A.
Contributors xix

1
Clinical Approach to Fever in Critical Care
Burke A. Cunha
Infectious Disease Division, Winthrop-University Hospital, Mineola, New York,
and State University of New York School of Medicine, Stony Brook, New York, U.S.A.
INTRODUCTION
Fever is a cardinal sign of disease. It may be caused by a wide variety of infectious and
noninfectious disorders. The number of disorders that occur in seriously ill patients in critical
care units (CCUs) are more limited than in the non-CCU population. The main clinical
problems in the CCU are to differentiate between noninfectious and infectious causes of fever
and then to determine the cause of the patient’s fever.
The clinical approach to fever in the CCU is based on a careful analysis of the acuteness/
chronicity of the fever, the characteristics of the fever pattern, the relationship of the pulse to
the fever, the duration of the fever, and the defervescence pattern of the fever. It is the task of
the infectious disease consultant to relate aspects of the patient’s history, physical, laboratory,
and radiological tests with the characteristics of the patient’s fever, which together determine
differential diagnostic possibilities. After the differential diagnosis has been narrowed by
analyzing the fever’s characteristics and the patient-related factors mentioned, it is usually
relatively straightforward to order tests to arrive at a specific diagnosis.
Most patients in the CCU have some degree of temperature elevation. Trying to

determine the cause of fever in CCU patients is the daily task of the patient’s physicians. Fever
in the CCU can be a perplexing problem because the clinician must determine whether the
patient’s underlying disorder is responsible for the fever or fever is a superimposed phenomenon
on the patient’s underlying problem responsible for admission to the CCU. The infectious disease
consultant’s clinical excellence is best demonstrated by the rapidity and accuracy in arriving at a
causeforthepatient’sfever(Table1)(1–10).
CAUSES OF FEVER IN THE CCU
Noninfectious Causes of Fever in the CCU
A wide variety of disorders are associated with a febrile response. Both infectious and
noninfectious disorders may cause acute/chronic fevers that may be low, i.e., 1028F, or high
grade, i.e., !1028F. Of the multiplicity of conditions that may be encountered in the CCU with
a few notable exceptions, most noninfectious disorders are associated with fevers of 1028F.
Exceptions to the 1028F fever rule include malignant hyperthermia, adrenal insufficiency,
massive intracranial hemorrhage, central fever, drug fever, collagen vascular disease flare,
particularly systemic lupus erythematosus (SLE) flare, heat stroke, vasculitis, and certain
malignancies particularly lymphomas. The most common noninfectious disorders encoun-
tered in the CCU either have no fever, or have low-grade fevers 1028F, and include acute
myocardial infarction, pulmonary embolism/infarct, phlebitis, catheter-associated bacteriuria,
acute pancreatitis, viral hepatitis, acute hepatic necrosis, uncomplicated wound infections,
subacute bacterial endocarditis, cerebrovascular accidents (CVAs), sma ll/moderate intracerebral
bleeds, pulmonary hemorrhage, acute respiratory distress syndrome (ARDS), bronchiolitis
obliterans organizing pneumonia (BOOP), pleural effusions, atelectasis, cholecystitis, non-
infectious diarrheas, Clostridium difficile diarrhea, ischemic colitis, splenic infarcts, renal infarcts,
pericardial effusion, dry gangrene, gas gangrene, surgical toxic shock syndrome, acute gout,
small-bowel obstruction, and cellulitis (1,3,5,11– 31 ).
Extreme hyperpyrexia (temperature !1068F) is not a clue to an infectious disease. There
are relatively few disorders, all noninfectious, which are associated with extreme hyperpyrexia
(Table 2) (1,3,5).
The clinical approach to the noninfectious disorders with fever is usually relatively
straightforward because they are readily diagnosable by histo ry, physical, or routine

laboratory or radiology tests. By knowing that noninfectious disorders are not associated
with fevers >1028F, the clinician can approach patients with these disorders that have fevers
>1028F by looking for an alternate explanation. The difficulty usually arises when the patient
has a multiplicity of conditions and sorting out the infectious from the noninfectious causes
can be a daunting task (Tables 3 and 4) (1–6,10).
Table 2 Causes of Extreme Hyperpyrexia (High Fevers !1068F)
. Hypothalamic disease/dysfunction
. Central fevers (hemorrhagic, trauma, infection, malignancy)
. Malignant neuroleptic syndrome
. Malignant hyperthermia
. Drug fever (typically 1028F–1068F)
. Tetanus
Table 1 Causes of Fever in the CCU
System/Source Infectious causes Noninfectious causes
. Central nervous Meningitis
Encephalitis
Cerebral infarction
Cerebral hemorrhage
Seizures
. Cardiovascular Endocarditis
Intravascular device infection
Central Venous Catheter (CVC)-
associated bacteremia
Septic thrombophlebitis
Pacemaker infection
Postperfusion syndrome (CMV)
Myocardial infarction
Dressler’s syndrome
Postpericardiotomy syndrome
Thrombophlebitis

. Pulmonary Pneumonia
Empyema
Tracheobronchitis
Sinusitis
Deep vein thrombosis
Atelectasis
Chemical pneumonitis
Pulmonary emboli/infarction
. Gastrointestinal Intra-abdominal abscess
Cholecystitis/cholangitis
Viral hepatitis
Peritonitis
Diverticulitis
C. difficile colitis
Gastrointestinal hemorrhage
Acalculous cholecystitis
Nonviral hepatitis
Pancreatitis
Inflammatory bowel disease
Ischemic colitis
. Renal Urinary tract infection (Cystitis)
Acute pyelonephritis
. Rheumatologic Osteomyelitis
Septic arthritis
Gout/pseudogout
Collagen vascular disease (SLE)
Vasculitis
. Skin/soft tissue Cellulitis
Wound infection
Hematoma

Intramuscular injections
Burns
. Endocrine/metabolic Adrenal insufficiency
Hyperthyroidism/thyroiditis
. Miscellaneous Sustained bacteremias
Transient bacteremias
Parotitis
Pharyngitis
Alcohol/drug withdrawal
Drug fever
Postoperative/postprocedure
Blood/blood products transfusion
Intravenous contrast reaction
Fat emboli syndrome
Neoplasms/metastasis
2 Cunha
Table 3 Clinical Syndromic Approach to Fever in the CCU
Either community-acquired or
Usual maximum temperature
System Community-acquired fevers Nosocomial fevers nosocomial fever !1028F 1028F
CNS
Cardiovascular
. Meningitis
. Encephalitis
. Brain abscess
. SBE
. Viral pericarditis
. Neurosurgical shunt infection
. Posterior fossa syndrome
. CVC infections

. Lead/generator infected pacemaker
associated infections
. Postpericardiotomy syndrome
. Postperfusion syndrome (CMV)
. “Balloon pump fever”
. Sternal osteomyelitis
. Central fevers
. CVAs
. Massive ICH
. Seizures
. ABE
{
. Myocardial infarction
. Myocardial/ perivalvular abscess
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ

þ
þ
þ
þ
(Continued)
Clinical Approach to Fever in Critical Care 3
Table 3 Clinical Syndromic Approach to Fever in the CCU (Continued )
Either community-acquired or
Usual maximum temperature
System Community-acquired fevers Nosocomial fevers nosocomial fever !1028F 1028F
Pulmonary
GI
. CAP
. Lung abscess
. Empyema
. SLE pneumonitis
. BOOP
. Bronchogenic carcinomas
(without postobstructive
pneumonia)
. Pulmonary cytoxic drug
reactions
. Cholecystitis
. Ischemic colitis
. VAP
. Mediastinitis
. Pulmonary emboli/infarction
. Pleural effusion
. Atelectasis
. Dehydration

. Tracheobronchitis
. Cholangitis
. Viral hepatitis
. Acalculous cholecystitis
. Peritonitis
. Pancreatitis
. Intra-abdominal abscess
. GI hemorrhage
. C. difficile diarrhea
. C. difficile colitis
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ
þ

þ
þ
þ
þ
þ
4 Cunha