Table Of ContentANTIMICROBIAL
RESISTANCE
A Crisis in Health Care
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, Swte University of New York at Buffalo
!RUN R. COHEN, The Weizmann Institute of Science
DAVID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research
RODOLFO PAOLETTI, University of" Milan
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ANTIMICROBIAL
RESISTANCE
A Crisis in Health Care
Edited by
Donald L. Jungkind
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania
Joel E. Mortensen
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania
Henry S. Fraimow
The Graduate Hospital
Philadelphia, Pennsylvania
and
Gary B. Calandra
Merck Research Laboratories
West Point, Pennsylvania
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Llbrary of Congress Catalog1ng-1n-Pub11cat1on Data
Antimicrobial reststance a crisis in health care I edited by Donald
L. Jungk 1nd ... [et a I. J.
p. cm. -- CAdvances in experimental medicine and blology ; v.
390)
''Based an the proceedings of the Eastern Pennsylvania Branch of
the American Soc1ety of Microb1ology Sympos1um an Antlmicrobial
Res1stance: a Crisls 1n Healthcare--Cilnlcal Labaratory and
Epidemiologie Considerations. held November 11-12, 1993 in
Philadelphia, Pennsylvania"--T.p. verso.
Includes bibliograph1cal references and Index.
ISBN 978-1-4757-9205-8 ISBN 978-1-4757-9203-4 (eBook)
DOI 10.1007/978-1-4757-9203-4
1. Antibiotics--Congresses. 2. Drug res1stance 1n m1croorgan1sms-
-Congresses. I. Jungkind, Donald L. II. Eastern Pennsylvania
Branch of the American Saciety of Microblology Symposium an
Antimicrabial Resistance: a Crisis in Healthcare--Clinical
Labaratory and Epidem1o1og1c Considerations <1993 Philadelphia,
Pa. l III. Series.
[ONLM: 1. Drug Resistance. Microbial--congresses.
2. Streptococcal Infectians--drug therapy--congresses. W1 AD559
v.390 1995 I QW 52 A6313 1995]
RM267.A556 1995
616' . o1 --dc20
DNLM/DLC
far Library af Congress 95-48271
CIP
Basedon the proceedings of the Eastern Pennsylvania Branch of the American Society of Microbiology
Symposium on Antimicrobial Resistance: A Crisis in Healthcare-Clinical Laboratory and
Epidemiologie Considerations, held November 11-12, 1993, in Philadelphia, Pennsylvania
ISBN 978-1-4757-9205-8
© 1995 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1995
Softcoverreprint ofthe hardcoverIst edition 1995
10987654321
All rights reserved
No part ofthis book may be reproduced, stored in a retrieval system, or Iransmitted in any form or by
any means, electronic, mechanical, photocopying. microfilming, rccording, or otherwise, without
written permission from the Publisher
DEDICATIONS
Donald L. Jungkind dedicates his contributions to his wife Kim, to his
parents, and to George Wren, Robert C. Wood, and Gerald Shockman, who
were influential in his education in science and antimicrobial agents.
Henry S. Fraimow dedicates his contributions to his wife Jacqueline
French, to his children, Benjamin and Rebecca, and to Michael Miller.
Joel E. Mortensen dedicates his contributions to the staff of the Clinical
Microbiology Laboratory at St. Christopher's Hospital for Children, and to
his son Jonathan.
Dr. Gary B. Calandra dedicates his contributions to his wife Kathie and to
his son John.
GENEROUS SUPPORT FOR THE SYMPOSIUM THAT WAS
THE BASIS FOR TmS PUBLICATION WAS PROVIDED BY
Sponsoring Organization
Eastern Pennsylvania Branch of the American Society for
Microbiology
Corporate Sponsors
Lederle Laboratortes
Merck, Inc.
Miles Pharmaceuticals
Pfizer Roertg Division
MetPath
Becton-Dickinson
Pfizer Laboratortes
Ortho Pharmaceuticals
Remel Microbiology Products
Baxter-Micro scan
Academic Sponsors
Pennsylvania Department of Health
Gwynedd-Mercy College
Hahnemann University
National Laboratory Training Network
Pennsylvania College of Podiatrtc Medicine
Philadelphia College of Osteopathic Medicine
St. Chrtstopher's Hospital
Temple University School of Medicine
Thomas Jefferson University
University of Pennsylvania
PREFACE
Development and Implications of Antimicrobial Resistance
One of the most ominous trends in the field of antimicrobial
chemotherapy over the past decade has been the increasing pace of
development of antimicrobial resistance among microbial pathogens.
The hypothesis that man can discover a magic bullet to always cure a
particular infection has proved false. Physicians are now seeing and
treating patients for which there are few therapeutic alternatives, and in
some cases, none at all. Until recently there was little concern that
physicians might be losing the war in our ability to compete with the
evolving resistance patterns of microbial pathogens. Now the general
public is very aware of the threat to them if they become infected,
thanks to cover story articles in major magazines such as Time,
Newsweek, newspapers, and other news sources.
Antimicrobial resistance is not a novel problem. Shortly after the
widespread introduction of penicillin in the early 1940s, the first strains
of penicillin-resistant staphylococci were described. Today it is an
uncommon event for a clinical laboratory to isolate an S. aureus that is
sensitive to penicillin. Other gram-positive strains of bacteria have
become resistant, including the exquisitely sensitive Streptococcus
pneumoniae. Sensitivity to vancomycin was once so uniform that it was
used in routine clinical laboratories as a surrogate marker for whether
an organism should be classified as a gram-positive. That criterion can
no longer be relied upon because of emerging resistance among some
species. Gram-negative bacteria, viruses, fungi, and parasites all have
succeeded in developing resistance.
The worldwide pharmaceutical industry has created more than 50
penicillins, 70 cephalosporins, 12 tetracyclines, 8 aminoglycosides, and
multiple quinolones, monobactams, carbepenems, macrolides, and
dihydrofolate reductase inhibitors. Despite all of these agents, patients
still succumb to bacterial infections caused by bacterial strains that
have learned to beat the antibiotics. The origins of the current crisis in
antimicrobial resistance are complex and may differ somewhat for
nosocomial and community-acquired pathogens and for highly
developed and underdeveloped countries. However, resistance should
be considered the natural consequence of microorganisms responding
to the selective pressures of antimicrobial agents, and this process will
continue to occur as long as antimicrobial agents are in use. The
consequences of increasing resistance are enormous. Resistance leads
to increased morbidity and mortality, the need to use more toxic and
Vii
expensive therapies, and to expend ever greater resources on
monitoring and surveillance, all at a time when resources for health
care are becoming more limited.
We need to understand how resistance develops, how it spreads,
how the practice of medicine affects resistance, and respond to this
threat before we return to a preantibiotic era of medicine. This process
will require the cooperation of physicians, researches, public health
officials, the pharmaceutical industry, the food industry, and the
cooperation of governments throughout the world, to win against, or at
least keep pace with, an increasingly complex population of microbes.
This symposium was organized to bring together physicians,
researchers, microbiologists, and laboratorians with recognized experts
in the field of antimicrobial resistance to further the understanding of
this complex issue. The presenters of this symposium have highlighted
varied aspects of the problem. Most importantly they have, in key
areas, given direction to address the problems associated with
antimicrobial resistance, with immediate action steps and future
research. In the months since the symposium presentations, the
chapters for this book were written, reviewed, and updated as
necessary, to insure that the information is timely and relevant. We
hope the papers will stimulate further action by the readers.
ACKNOWLEDGMENT. The editors wish to thank Paul R. Jaselskis for his
patience and tireless efforts in the administrative preparation of these
manuscripts. His influence is evident throughout the book. A big
''Thanks," Paul!
Donald L. Jungkind
Henry S. Fraimow
Joel E. Mortensen
Gary B. Calandra
viii
CONTENTS
Antimicrobial Resistance: A Global Perspective 1
STUART B. LEVY
Resistance to Antibacterial Agents. . . . . . . . . . . . . . . . . . . . . . . . 15
CHRISTINE C. SANDERS and W. EUGENE SANDERS, JR.
Bacterial Resistance to Carbapenems . . . . . . . . . . . . . . . . . . . . . . 25
DAVID M. LIVERMORE
Bacterial Resistance to Fluoroquinolones: Mechanisms and
Patterns ............................................ 49
DAVID C. HOOPER
A Comparison of Active Site Binding of 4-Quinolones and Novel
Flavone Gyrase Inhibitors to DNA Gyrase . . . . . . . . . . . . . . . . . . . 59
J.J. HILLIARD, H.M. KRAUSE, J.I. BERNSTEIN, J.A.
FERNANDEZ, V. NGUYEN, K.A. OHEMENG, and J.F. BARRETT
A Low-Copy Number Plasmid Mediating f3-Lactamase Production
by Xanthomonas maltophilia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
MICHAEL D. KELLY and JOEL E. MORTENSEN
Glycopeptide Resistance in Gram-Positive Pathogens. . . . . . . . . . 81
HENRYS. FRAIMOW and DAVID M. SHLAES
Vancomycin-Dependent Enterococci: A Clinical and Laboratory
Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
HENRY S. FRAIMOW and DONALD L. JUNGKIND
Streptococcus pyogenes: Resistant. Tolerant, Neither or Both? . . . 109
JOEL E. MORTENSEN and THOMAS MCDOWELL
The Antimicrobial Susceptibility of Streptococcus pyogenes
Isolates from the Philadelphia Area. . . . . . . . . . . . . . . . . . . . . . . . 119
ANTHONY L. FERRARO, JOEL E. MORTENSEN, DEBORAH L.
BLECKER,andCHANHPHENGPHENGVATH
Antibiotic-Resistance in Streptococcus pneumoniae. . . . . . . . . . . 123
KAREN KRISHER
ix
