Table Of ContentImmunology and Infectious Disease
MOLECULAR AND CELLULAR BIOLOGY
OF CRITICAL CARE MEDICINE
Robert S. B. Clark and Joseph A. Carcillo, Series Editors
1. H. R. Wong and T. P. Shanley (eds.): Molecular Biology of Acute
Lung Injury. 2001. ISBN: 0-7923-7434-7
2. R.S.B. Clark and P. Kochanek (eds.): Brain Injury. 2001.
ISBN: 0-7923-7532-7
3. L.A. Doughty and P. Linden (eds.): Immunology and Infectious
Disease. 2002. ISBN: 1-4020-7307-0
IMMUNOLOGY AND INFECTIOUS DISEASE
edited by
Lesley A. Doughty, M.D.
Pediatric Critical Care Medicine
Rhode Island Hospital
Providence, RI
and
Peter Linden, M.D.
Critical Care Medicine/Infectious Disease
University of Pittsburgh Medical Center
Pittsburgh, PA
Springer Science+Business Media, LLC
Library of Congress Cataloging-in-Publication Data
A C.I.P. Catalogue record for this book is available
from the Library of Congress.
ISBN 978-1-4613-4984-6 ISBN 978-1-4615-0245-6 (eBook)
DOI 10.1007/978-1-4615-0245-6
Immunology and Infectious Disease
Edited by: Lesley A. Doughty and Peter Linden
Copyright © 2003 by Springer Science+Business Media New York
Originally published by Kluwer Academic Publishers in 2003
Softcover reprint of the hardcover 1s t edition 2003
All rights reserved. No part ofthis work may be reproduced, stored in a retrieval
system, or transmitted in any form or by any means, electronic, mechanical,
photocopying, microfilming, record ing, or otherwise, without the written
permission from the Publisher, with the exception of any material supplied
specifically for the purpose of being entered and executed on a computer system,
for exclusive use by the purchaser of the work.
Printed on acid-free pap er.
CONTENTS
List of Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. vii
CHAPTERS
1. Host Microbicidal Actions of the Innate Immune Response .......1
Steven M. Opal, M.D. and Richard L. Yap, M.D.
2. Activation of the Innate Immune Response in Critical Illness .... 19
Andreas Oberholzer, Caroline Oberholzer, and Lyle L. Moldawer
3. Down-Regulation of the Immune Response ....................4 1
Alfred Ayala, Chun-Shiang Chung, Grace Y. Song, Patricia S.
Grutkoski, and H. Hank Simms
4. Mechanisms of Pharmacologic Immune Suppression ...........7 9
Barry D. Kahan, Ph.D., M.D.
5. Modulation of the Immune Response in Critical IIInessllnjury .. 115
Lesley A. Doughty, M.D.
6. Immune Monitoring and Strategies for Immune Modulation ... 155
Hans-Dieter Yolk, Heidrun Zuckermann, Wolfgang Kox, Christian
Woiciechowsky, Conny Hoeflich, Christian Meisel, Gerald Gruetz,
Wolf-Dietrich Docke, Petra Reinke
7. Central Venous Catheter Related Infections: The Role of
Antimicrobial Catheters ..................................1 87
Ioannis Chatzinikolaou and Issam I. Raad
8. Discrimination of True Lower Respiratory Tract Infection
in the Mechanically Ventilated Patient ......................2 17
Richard G. Wunderink and Grant W. Waterer
9. Detection of Urinary Tract Infection in the Catheterized ICU
Patient .................................................2 41
Paul A. Tambyah and Dennis G. Maki
10. Antimicrobial Choices and Dosing Strategies to Maximize
Efficacy and Minimize the Development of Bacterial
Resistance ..............................................2 57
Joseph A. Paladino, PharmD
Contributors
Alfred Ayala, Ph.D. Gerald Gruetz
Center for Surgical Research Department of Medical
Rhode Island Hospital Immunology
593 Eddy Street University Hospital
Providence, RI 02903 Charite, Humboldt-University
Berlin, Germany
Ioannis Chatzinikolaou, M.D.
Department of Infectious Patricia S. Grutkoski
Diseases Division of Surgical Research
Infection Control and Employee Department of Surgery
Health Brown University School of
The University ofTexasl Medicine
M.D. Anderson Cancer Center Providence,RI 02903
Houston, TX
Conny Hoeflich
Chun-Shiang Chung Department of Medical
Division of Surgical Research Immunology
Department of Surgery University Hospital
Brown University School of Charite, Humboldt-University
Medicine Berlin, Germany
Providence,RI 02903
Barry D. Kahan, Ph.D., M.D.
Wolf-Dietrich Docke Director, Division of
Department of Medical Immunology
Immunology And Organ Transplantation
University Hospital University of Texas Medical
Charite, Humboldt-University School
Berlin, Germany 6431 Fannin
Room 6.240
Lesley A. Doughty, M.D. Houston, TX 77030
Department of Pediatrics
Division of Pediatric Critical Care Wolfgang Kox
Medicine Department of Anaesthesiology
Rhode Island Hospital and Intensive Care
593 Eddy Street University Hospital
Providence, RI 02903 Charite, Humboldt-University
Berlin, Germany
Vlll
Dennis G. Maki Steven Opal, M.D.
Section of Infectious Diseases Infectious Disease Division
(DGM) Memorial Hospital of Rhode
Department of Medicine Island
University of Wisconsin 111 Brewster Street
Medical School Pawtucket, RI 02860
University of Wisconsin-Madison
Madison, WI Joseph A. Paladino, PharmD
State University of New York at
Christian Meisel Buffalo
Department of Medical CPL Associates, LLC
Immunology Amherst NY 14226-1727
University Hospital
Charite, Humboldt-University Issam I. Raad
Berlin, Germany Department of Infectious
Diseases
Lyle L. Moldawer, Ph.D. Infection Control and Employee
Department of Surgery Health
University of Florida The University of Texasl
College of Medicine M.D.Anderson Cancer Center
Gainesville, FL 32608 Houston, TX
Andreas Oberhoizer, M.D. Petra Reinke
Department of Trauma and Department of Nephrology and
Reconstructive Surgery Internal Intensive Care
Benjamin Franklin Medical University Hospital Charite,
Center Humboldt-University
Freie Universitat Berlin, Germany
Berlin, Germany
H. Hank Simms, M.D.
Caroline Oberhoizer, M.D. Division of Surgical Research
Department of Trauma and Department of Surgery
Reconstructive Surgery, Brown University School of
Benjamin Franklin Medical Medicine
Center Providence, RI 02903
Freie Universitat
Berlin, Germany
IX
Grace Y. Song Richard G. Wunderink, M.D.
Division of Surgical Research Research Department
Department of Surgery Methodist Le Bonheur Healthcare
Brown University School of University of Tennessee
Medicine Memphis, TN
Providence, RI 02903
Richard L. Yap, M.D.
Paul A. Tambyah, M.D. Brown University School of
Department of Medicine (PAT) Medicine
National University of Singapore Providence, RI 02903
Medical School
Singapore Heidrun Zuckermann
Department of Surgery
Hans-Dieter Yolk, M.D. University Hospital Charite,
Institute of Medical Immunology Humboldt-University
Charite-Campus Mitte Berlin, Germany
D 10 090, Berlin
Germany
Grant W. Waterer
Respitatory Medicine
Department of Medicine
University of Weste m Australia
1
HOST MICROBICIDAL ACTIONS OF THE
INNATE IMMUNE RESPONSE
Steven M. Opal, M.D. and Richard L. Yap, M.D.
Brown University School ofM edicine, Providence, Rhode Island 02903
INTRODUCTION
The human body is constantly under assault by potential microbial
pathogens. In addition to the enonnous numbers of micro-organisms that
we ingest, inhale, aspirate, and come in direct contact with on a daily basis,
the average human has 1014 (one hundred trillion) micro-organisms in the
alimentary tract and on epithelial surfaces throughout the body (1).
Transient bacteremia is a frequent event from oral microbial flora or skin
flora following minor trauma to these areas (e.g. 25% incidence of
bacteremia with brushing teeth) (2). A multitude of fungal spores are
inhaled on a daily basis and humans are repeatedly exposed to potentially
pathogenic respiratory viruses in the environment. Our very existence is
absolutely dependent upon an ever vigilant and efficient antimicrobial
defense system. In this introductory chapter, we will review the
fundamental elements of the host defense system and describe the basic
strategies employed against bacteria, viruses, and fungi.
ESSENTIAL COMPONENTS OF THE NON-IMMUNE
ANTIMICROBIAL DEFENSE SYSTEM
The first line of defense against microbial pathogens is an intact
integument, functioning mucous membrane system, and mechanical
clearance and motility systems (3). The physical barrier provided by the
epithelial surface is complemented by non-specific antimicrobial molecules
such as lysozyme, low gastric pH, bile acids, free fatty acids, cationic
antimicrobial peptides, and iron sequestering proteins which protect the
integument from invasion by microbial pathogens.
Breaks in the integument induced by intravenous catheters, urinary
catheters, surgery or trauma, and skin breakdown from skin eruptions, skin
2 Host Microbicidal Actions
maceration, pressure ulcers, etc ... are all too common in the leU patient.
These breaks in epithelial membranes immediately places the patient at
increased risk from infection in the leu setting. The importance of an
intact physical barrier and mechanical clearance against microbial
pathogens as a defense strategy against infection cannot be over
emphasized. Cough, mucociliary mucous transport, peristalsis, urinary
flow, and constant shedding of surface epithelial cells with attached
microbial flora are among the most important antimicrobial defense
strategies found within the human physiology.
Unfortunately, many of these clearance mechanisms and physical barriers
are violated during the standard care of a critically ill patient. Endotracheal
tubes are placed along with urinary catheters, vascular catheters, anti
motility agents, inhibitors of gastric acidity, and intestinal ileus typify the
leu patient. As such, the leu patient is already in a compromised position
with respect to interactions with potential human pathogens. For this and
other reasons, infection is an omnipresent risk in critical care medicine.
Every effort should be made to limit this risk in the care of the leu patient.
IMMUNE DEFENSE MECHANISMS AGAINST
MICROBIAL INVASION
The human immune response is divisible into the innate immune defense
system and the acquired or adaptive immune system. The innate immune
system is a phylogenetically ancient system that provides a rapid response
system to a multitude of potential microbial challenges. This intricate
system is non-specific by nature in order to provide a first line of defense
against a myriad of potential pathogens (4). The adaptive system is
fundamentally a highly specific immune system that responds rigorously
and with great precision against specific antigens to which the host has been
exposed to from the environment. The adaptive immune response is further
subdivided into B lymphocyte-plasma cell responses (antibody responses -
humoral immunity) and T cell responses (cell-mediated immune responses).
The innate and the adaptive immune response will be discussed in
considerable detail in the following chapters of this book. The remainder of
this chapter will focus upon general approaches for removal of specific
groups of microbial pathogens by specific cell types.
The innate immune response has a number of critically important cellular
and humoral elements that provide defense against microbial invasion. This
