Antibiotics in laboratory medicine

898 Pages·2005·19.84 MB·English

by  Victor Lorian MD

Antibiotics in Laboratory
Medicine

5th Edition
2005
Lippincott Williams & Wilkins
Philadelphia
530 Walnut Street, Philadelphia, PA 19106 USA http://www.lww.com/
0-7817-4983-2
Fourth Edition, © 1996 Williams & Wilkins
Third Edition, © 1991 Williams & Wilkins
Second Edition, © 1986 Williams & Wilkins
First Edition, © 1980 Williams & Wilkins
All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form or by any means, including
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Library of Congress Cataloging-in-Publication Data
Antibiotics in laboratory medicine / [edited by] Victor Lorian.—5th ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 0-7817-4983-2
1. Microbial sensitivity tests. 2. Antibiotics—Analysis. 3. Drug resistance in microorganisms. I. Lorian, Victor.
[DNLM: 1. Microbial Sensitivity Tests. 2. Anti-Bacterial
Agents—pharmacology. QW 25.5.M6 A629 2005]
QR69.A57A57 2005
615′.329—dc22
2004027260
Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices. However, the
authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in
this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the
publication. Application of this information in a particular situation remains the professional responsibility of the practitioner.
The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in
accordance with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in
government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the
package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly
important when the recommended agent is a new or infrequently employed drug.
Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in
restricted research settings. It is the responsibility of health care providers to ascertain the FDA status of each drug or device planned for
use in their clinical practice.
10 9 8 7 6 5 4 3 2 1
Dedication
To Marina Lorian, wife, companion, and friend, with love and appreciation. Her constant support and inspiration have made my career
accomplishments possible and contributed to the realization of this work.
Editor
Victor Lorian M.D.
Professor of Laboratory Medicine
RET., Albert Einstein College of Medicine, New York
Secondary Editors
Frances Destefano
Acquisitions Editor
Mike Standen
Developmental Editor
Alicia Jackson
Project Manager
Benjamin Rivera
Senior Manufacturing Manager
Kathy Neely
Marketing Manager
Teresa Mallon
Designer
Production Service: TechBooks
Printer: Edwards Brothers
Contributing Authors
Paul G. Ambrose Pharm. D.
Associate Research Professor
Pharmacy Practice, School of Pharmacy and Pharmaceutical Services, University at Buffalo, Amherst, NY
Daniel Amsterdam M.D., Ph.D.
Professor
Department of Microbiology, Medicine and Pathology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo,
Buffalo, New York
D. A. Andes
University of Wisconsin School of Medicine, Madison, Wisconsin
Joseph M. Ascenzi Ph.D.
Senior Manager
Regulatory Affairs, Advanced Sterilization Products, Irvine, California
David M. Bamberger M.D.
Professor
Department of Medicine, University of Missouri–Kansas City, Kansas City, Missouri
Jan M. Bell B.Sc.
Head
Antibiotic Research Laboratory, Women’s and Children’s Hospital, North Adelaide, South Australia
Robert A. Bonomo M.D.
Infectious Diseases Section, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio
Darcie L. Bridwell
Assistant Professor
Department of Medicine, University of Missouri–Kansas City, Kansas City, Missouri
Vincent Calvez M.D., Ph.D.
Professor of Virology
Department of Virology, Medical School of Pitié Salpêtriére, University of Pierre et Marie Curie, Paris, France
Pierre Dellamonica M.D., Ph.D.
Professor of Infectiology
Department of Infectious Diseases; Director of Laboratory of Infectious Diseases, Medical School of Nice, University of Nice Sophia-
Antipolis, Nice, France
Daniel J. Diekema M.D., M.S.
Clinical Associate Professor
Department of Internal Medicine and Pathology, University of Iowa College of Medicine, Iowa City, Iowa
Stephen C. Edberg Ph.D.
Professor
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
George M. Eliopoulos M.D.
Professor of Medicine
Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Martin S. Favero Ph.D.
Director
Scientific and Clinical Affairs, Advanced Sterilization Products, Irvine, California
John W. Foxworth
Associate Professor
Department of Medicine, University of Missouri–Kansas City School of Medicine, Kansas City, Missouri
N. Frimodt-Møller
Microbiological Research and Development, Statens Serum Institute, Copenhagen, Denmark
Thomas R. Fritsche M.D., Ph.D.
Associate Director
The JONES Group/JMI Laboratories, North Liberty, Iowa
Dale N. Gerding M.D.
Professor
Department of Medicine, Loyola University Chicago, Maywood, Illinois
David W. Hecht M.D.
Professor of Medicine; Chief
Division of Infectious Diseases, Loyola University Stritch School of Medicine, Hines Medical Center, Maywood, Illinois
Margareta Ieven M.D.
Associate Professor
Department of Medical Microbiology, University Hospital Antwerp, Antwerp, Belgium
Clark B. Inderlied Ph.D.
Professor of Clinical Pathology
University of Southern California, Keck School of Medicine, Children’s Hospital Los Angeles, Los Angeles, California
Ronald N. Jones M.D.
Director
International Surveillance Programs, The JONES Group/JMI Laboratories, North Liberty, Iowa; Adjunct Professor Department of Medicine,
Tufts University School of Medicine, Boston, Massachusetts
Roger D. Klein M.D., J.D.
Clinical Fellow in Microbiology and Virology
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
Bruno Lina M.D., Ph.D.
Professor of Virology
University of Claude Bernard; Deputy–Chief, Virology Laboratory of Hospices Civils of Lyon, Rockefeller University, Lyon, France
Anne-Geneviève Marcelin Pharm.D., Ph.D.
Doctor of Virology
Department of Virology, Pitié-Salpêtrière Hospital, Medical School of Pitié-Salpêtrière, University of Pierre and Marie Curie, Paris, France
Marie-Christine Mazeron M.D., Ph.D.
Laboratory of Virology/Bacteriology, Lariboisière Hospital, Medical School of Lariboisière Saint-Louis, University of Paris, Paris, France
Robert C. Moellering Jr. M.D.
Herman L. Blumgart Professor of Medicine
Harvard Medical School; Physician-in-Chief and Chairman, Department of Medicine, Beth Israel Deacaness Medical Center, Boston,
Massachussetts
Kevin A. Nash Ph.D.
Assistant Professor
Department of Pathology, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California
Terry O’Reilly Ph.D.
Novartis Institute for Biomedical Research, Basel, Switzerland
Ch. Østergaard
Statens Serum Institute, Copenhagen, Denmark
Michael A. Pfaller M.D.
Professor
Department of Pathology; Director, Department of Molecular Epidemiology and Fungus Testing Laboratory, University of Iowa College of
Medicine, and College of Public Health, Iowa City, Iowa
Satish K. Pillai M.D.
Clinical Fellow in Medicine
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachussetts
Didier Raoult M.D., Ph.D.
Professor
Marseilles Medical School; Director of Rickettsia Unit, Marseilles, France
Louis B. Rice M.D.
Case Western Reserve University School of Medicine; Chief, Infectious Diseases Section, Veterans Administration Medical Center,
Cleveland, Ohio
Michael G. Rinaldi Ph.D.
Professor of Pathology and Medicine
University of Texas Health Science Center at San Antonio; Director, Department of Veterans Affairs Mycology Reference Laboratory, Audie
L. Murphy Memorial Veterans Hospital, San Antonio, Texas
Pierre-Marie Roger M.D., Ph.D.
Doctor of Infectiology
Department of Infectious Diseases, Medical School of Nice, University of Nice Sophia-Antipolis, Nice, France
Jean-Marc Rolain Pharm.D., Ph.D.
Unité des Rickettsies, Faculté de Médecine, Université de la Mediterranée, Marseille, France,
Helio S. Sader M.D., Ph.D.
Director
International Surveillance Program, The JONES Group/JMI Laboratories, North Liberty, Iowa; Professor, Division of Infectious Diseases,
Federal University, Sao Paulo, Brazil
Christopher S. Shain Pharm.D.
Assistant Professor in Clinical Pharmacology
University of Missouri–Kansas City, School of Medicine, Kansas City, Missouri
Charles W. Stratton IV M.D.
Professor
Departments of Pathology and Medicine, Vanderbilt University; Director, Clinical Microbiology Lab, Vanderbilt University Medical Center,
Nashville, Tennessee
Albert Tran M.D., Ph.D.
Professor in Hepato-Gastroenterology; Director of Hepato-Gastroenterology Federation
Medical School of Nice, University of Nice Sophia-Antipolis, Nice, France
John D. Turnidge M.B.B.S., FRACP, FRCPA
Clinical Professor of Pathology and Pediatrics
University of Adelaide; Director, Microbiology and Infectious Diseases; Chief, Division of Laboratory Medicine, Women’s and Children’s
Hospital, North Adelaide, Australia
Matthew A. Wikler M.D.
Chief Medical Officer and Executive Vice President
Peninsula Pharmaceuticals, Inc., Alameda, California; Chairholder Subcommittee on Antimicrobial Susceptibility Testing, National
Committee for Clinical Laboratory Procedures
Preface
The antibiotic era is now 65 years old, and for the past 25 years Antibiotics in Laboratory Medicine has tracked the development of new
compounds and classes of antimicrobial agents and presented detailed methods and approaches for evaluating the efficacy and the
mechanisms of action and resistance of these compounds in vitro and in vivo.
In this, the fifth edition, the first of the new millennium, I am cognizant of the limited development of new antimicrobial agents, although I
have witnessed the expansion of new classes of anti-infective compounds, namely, antifungal and antiviral agents. Increasingly, molecular
methods, computer algorithms, and complex statistical programs are relied on for evaluating the potency of new and old drugs or
comparing activity within classes of agents, selecting appropriate therapy, accurately identifying the genetic resistance of microorganisms,
and tracking resistance trends locally, nationally, and internationally. All three—methods, algorithms, and programs—are included in this
work.
Of the seventeen chapters that make up this volume, five are new contributions on recent subjects and concepts in this ever developing
field. The remaining chapters, expanded and reworked, represent current science and practice. In addition, the large number of
references, including citations of works published in 2004, will help relieve the reader of tedious literature searches and surveys.
Several aspects of the revised and newly added chapters are worth highlighting. In the opening chapter on breakpoint determination Drs.
Wikler and Ambrose set the tone for this volume. It lays out a rationale for establishing breakpoints that is meaningful and acceptable to
laboratorians and clinical practitioners. In Chapter 3, Dr. Daniel Amsterdam discusses the relevance and clinically predictive value of in
vitro antimicrobial susceptibility testing. In my estimation, this is the first time that the issues covered are addressed in a monograph on
this subject. Additionally, a new in vitro parameter, the MPC (mutant prevention concentration) is discussed, along with the impact of
quorum sensing genes on antibiotic resistance. In Chapter 11, Dr. Magareta Ieven describes in great detail the latest methods for the
detection of antibacterial resistance genes—methods applicable in the clinical laboratory. In an expanded and updated version of a chapter
that appeared in the fourth edition, Dr. Charles Stratton discusses and interprets the molecular mechanisms of action for all antimicrobial
classes, with particular emphasis on the newer effects of cell wall activity by aminoglycosides. His explanations are truly original and
illuminating. The antivirogram, discussed by Dr. Pierre Dellamonica and colleagues in Chapter 13, is analogous to the antibiogram. It can be
used to compare the potency of antiviral compounds against HIV and explain the molecular action mechanisms of antiviral agents. In
Chapter 14, on disinfectants and antiseptics, Drs. Ascenzi and Favero present groundbreaking evidence and bring together the current state
of knowledge of these compounds and their modes of action, strategies for use, spectrum of activity, and mechanisms of resistance. For
the first time, the molecular link between these chemical disinfectants, sterilants, and antibiotics is established. Chapter 16, by Dr. David
Bamberger and coauthors, discusses the level of antibiotics in most tissues and body fluids. It has been brought completely up to date and
will be a vital resource for clinical practitioners. Lastly, the contribution of Drs. Thomas Fritsche, Helio Sader, and Ronald Jones describes
the dynamic epidemiological patterns in antibiotic resistance regionally, nationally, and internationally. Regularly published data from
several ongoing trending programs are presented.
During the past 25 years, I have often been reminded of the talented investigators who contributed to make the editions of this book
scientifically sound and clinically meaningful. The fifth edition is authored by distinguished physicians and scientists who are experts in
their particular areas, brilliant in their vision, and recognized worldwide. I am pleased to welcome the new authors and wish to thank them
not only for their important contributions but for their patience and courteous response to my many requests and queries during the editing
process.
It is fitting and appropriate that I express my gratitude and appreciation to those who have made my effort in completing this work truly
rewarding. Of special note are the efforts and counsel of Dr. Daniel Amsterdam in discussions of the subject matter as well as his
availability for resolution of several issues related to the preparation of this work. His contributions had a direct impact on the editing
process. I also wish to acknowledge the interest, competence, and intense dedication of Mr. Mike Standen of Lippincott, Williams & Wilkins
in the preparation of this manuscript for publication.
Victor Lorian M.D.
New York
Contents
Dedication
Authors
Preface
Contents
Chapter 1 The Breakpoint
Chapter 2 Antimicrobial Susceptibility on Solid Media
Chapter 3 Susceptibility Testing of Antimicrobials in Liquid Media
Chapter 4 Antimicrobial Susceptibility Testing of Anaerobic Bacteria
Chapter 5 Antimycobacterial Agents: In Vitro Susceptibility Testing and Mechanisms of Action and Resistance
Chapter 6 Antifungal Drugs: Mechanisms of Action, Drug Resistance, Susceptibility Testing, and Assays of Activity in Biological Fluids
Chapter 7 Antimicrobial Susceptibility Testing for Some Atypical Microorganisms (Chlamydia, Mycoplasma, Rickettsia, Ehrlichia,
Coxiella, and Spirochetes)
Chapter 8 Applications, Significance of, and Methods for the Measurement of Antimicrobial Concentrations in Human Body Fluids
Chapter 9 Antimicrobial Combinations
Chapter 10 Genetic and Biochemical Mechanisms of Bacterial Resistance to Antimicrobial Agents
Chapter 11 Molecular Methods for the Detection of Antibacterial Resistance Genes
Chapter 12 Molecular Mechanisms of Action for Antimicrobial Agents: General Principles and Mechanisms for Selected Classes of
Antibiotics
Chapter 13 The Antivirogram and the Modes of Action of Antiviral Agents, HIV, Hepatitis, Influenza, and Cytomegalovirus
Chapter 14 Disinfectants and Antiseptics, Modes of Action, Mechanisms of Resistance, and Testing
Chapter 15 Evaluation of Antimicrobials in Experimental Animal Infections
Chapter 16 Extravascular Antimicrobial Distribution and the Respective Blood and Urine Concentrations in Humans
Chapter 17 Epidemiology of Antimicrobial Resistance: Species Prevalence, Susceptibility Profiles, and Resistance Trends
Index
P.1
Chapter 1
The Breakpoint
Matthew A. Wikler
Paul G. Ambrose
WHAT IS A BREAKPOINT?
A breakpoint, in its simplest terms, represents the concentration of an antimicrobial that separates populations of microorganisms.
Breakpoints are used in many ways, and so there may be more than one breakpoint for a specific antimicrobial-microorganism combination.
It is also of interest that a breakpoint may change from time to time for a variety of reasons, as discussed later. In addition, breakpoints
can vary from one country to another and from one official body to another (e.g., the National Committee for Clinical Laboratory Standards
[NCCLS] versus the Food and Drug Administration [FDA]) within the same country. The determination of a specific breakpoint is not a black-
and-white decision, as many factors must be considered when selecting breakpoints.
Breakpoints that are reported by clinical microbiology laboratories to assist physicians in selecting antimicrobial agents to treat patients
are commonly referred to as antimicrobial susceptibility test interpretive categories. A result of “susceptible” implies that an infection due
to the isolate may be appropriately treated with the dosage of an antimicrobial agent recommended for that type of infection and infecting
species. A result of “resistant” implies that the isolate is not inhibited by the usually achievable concentrations of the agent with normal
dosage schedules and/or falls in the range where specific microbial resistance mechanisms are likely and clinical efficacy has not been
reliably attained in treatment studies. A result of “intermediate” implies that an infection due to the isolate may be appropriately treated
in body sites where the drugs are physiologically concentrated or when a high dosage of the drug can be used. The category of
“intermediate” is also used as a “buffer zone” to prevent small, uncontrolled technical factors from causing major discrepancies in
interpretations (21).
WHY DO WE NEED BREAKPOINTS?
Ultimately, the purpose of breakpoints is to provide clinicians with vital information to assist in making decisions about antimicrobial
treatments for patients with infections. Breakpoints serve many purposes, some of which are important for an individual patient, others for
epidemiological reasons. If breakpoints did not result in better patient care, then there would be little need to determine them, other than
as an academic exercise.
The remainder of this chapter focuses on breakpoints for bacteria, as these are currently the most advanced, and many of the principles
apply to the setting of breakpoints for other types of microorganisms.
THE HISTORY OF BREAKPOINT SETTING
NCCLS has been setting standards for the testing of bacteria and breakpoints since 1975. Initially, breakpoints were set by examining
scatterplots of the distributions of bacteria versus the results of susceptibility testing conducted with antibacterial agents. Such
scatterplots would frequently divide the bacteria into two populations, one of which would appear to be more susceptible to the
antibacterial being tested, the other less susceptible. The breakpoint would be the value separating the two populations. Setting
breakpoints in such a manner is probably suitable for epidemiologic purposes, as it allows one to easily determine shifts in the populations
of organisms and to identify the emergence of resistant populations. From a clinical perspective, however, such an approach does not take
into account the clinical implications.
In an attempt to improve the manner of setting breakpoints, NCCLS put together a working group to develop a document to provide
guidelines on how to determine