Impacts of Antibiotic-Resistant Bacteria (September - OTA Archive

187 Pages·1995·1.68 MB·English

by  Health Program

Impacts of Antibiotic-Resistant Bacteria
September 1995
OTA-H-629
GPO stock #052-003-01446-7
Recommended Citation: U.S. Congress, Office of Technology Assessment,
Impacts of Antibiotic-Resistant Bacteria, OTA-H-629 (Washington, DC: U.S.
Government Printing Office, September 1995).
F
oreword
P
enicillin, the first antibiotic, and the more than 100 other anti-
biotics now available to physicians are the primary weapons
in mankind's battle against bacterial diseases. They revolu-
tionized medicine, providing cures for formerly life-threaten-
ing diseases and preventing many previously inevitable deaths from
infected wounds. They still do, but within a short time of each antibi-
otic's introduction into medicine, some bacteria became resistant to it,
and the antibiotic lost its effectiveness against some diseases. Cur-
rently, few bacteria are resistant to all antibiotics, but many more are
resistant to all but one or all but a few antibiotics, and the expectation
is that resistant bacteria will continue to emerge and spread. The fear
is that many bacteria will become resistant to all antibiotics, plunging
humanity back into the conditions that existed in the pre-antibiotic
age.
OTA's report discusses what is known about the emergence and
spread of antibiotic-resistant bacteria and describes research and
development aimed at controlling those organisms. It concludes that
efforts are necessary both to preserve the effectiveness of currently
available antibiotics and to develop new antibiotics. It discusses issues
that arise in these activities, and it presents options for taking action.
This report was requested by the House Committee on Energy and
Commerce in the 103d Congress (now the House Committee on Com-
merce). The Senate Committee on Labor and Human Resources in the
same Congress endorsed the request for the study.
OTA was assisted in this study by an advisory panel of scientists
and physicians from academia, industry, and state government chaired
by Gail Cassell, Ph.D., of the University of Alabama at Birmingham.
OTA gratefully acknowledges the contribution of each advisory panel
member as well as that of many other experts who supplied informa-
tion for the report and participated in reviews of the report as it was
prepared. As with all OTA reports, the final responsibility for the con-
tent of the assessment rests with OTA.
ROGER C. HERDMAN
Director
iii
A
dvisory Panel
Gail Cassell, Ph.D. Prabhavathi B. Fernandes, Stuart Levy, M.D.
Professor and Chairman Ph.D. Professor of Medicine and of
Department of Microbiology Vice President, Drug Molecular Biology and
University of Alabama at Discovery Microbiology
Birmingham/University Biomolecular Screening Tufts University Medical
Station Bristol-Myers Squibb School
Birmingham, AL 35294 PO Box 4000 136 Harrison Ave.
Princeton, NJ 08543-4000 Boston, MA 02111-1800
Anne Bolmstrom
President Winston Frederick, M.D. Robert C. Moellering, Jr.,
AB Biodisk Infectious Disease Research M.D.
Pyramidvagon 7 Howard University Hospital Physician-In-Chief and
S-17136 Solna 2041 Georgia Ave., NW, Chairman
Sweden Room 5C-43 New England Deaconess
Washington, DC 20060 Hospital
Robert J. Bywater, Ph.D. Department of Medicine/Room
Director, Anti-Infective Joshua Lederberg, Ph.D. 6A
Assessment Professor 110 Francis Street
SmithKline Beecham Animal The Rockefeller University Boston, MA 02215-5553
Health New York, NY 10021-6399
Walton Oaks Barbara Murray, M.D.
Dorking Road Stephen Lerner, M.D. Professor of Medicine and of
Tadworth Professor of Medicine Microbiology and Molecular
Surrey KT20 7NT Wayne State University School Genetics
UK of Medicine Infectious Diseases
Harper Hospital/Division of University of Texas Medical
Barry Eisenstein, M.D. Infectious Diseases School at Houston
Vice President, Lilly Research 3990 John R 6431 Fannin
Labs Detroit, MI 48201 Houston, TX 77030
Lilly Corporate Center, 0434
Indianapolis, IN 46285
iv
Tom O'Brien, M.D. Alexander Tomasz, Ph.D. Craig Townsend, Ph.D.
Medical Director Professor and Head/Laboratory Chairman, Department of
Microbiology Laboratory of Microbiology Chemistry
Brigham and Women's The Rockefeller University The Johns Hopkins University
Hospital 1230 York Ave., Box 152 Charles and 34th Streets
75 Francis Street New York, NY 10021-6399 Baltimore, MD 21218
Boston, MA 02115
Richard Wenzel, M.D., M.Sc. Michael Zasloff, M.D., Ph.D.
Lone Simonsen, Ph.D. Associate Chairman President, Magainin Research
926 Waverly Way, Apt. A Department of Internal Institute
Atlanta, GA 30307 Medicine 5110 Campus Drive
The University of Iowa Plymouth Meeting, PA 19462
Harry Taber, Ph.D. Iowa City, IA 52242
Acting Director, Division of
Infectious Diseases
NY State Department of
Health
Wadsworth Center
David Axelrod Institute
PO Box 22002
Albany, NY 12201-2002
v
P
roject Staff
Clyde J. Behney PRIMARY STAFF David Frankel
Assistant Director, OTA The Lancet
Michael Gough
Project Director
Sean Tunis Sandra Handwerger
Health Program Director Rockefeller University
Elise Berliner
ADMINISTRATIVE STAFF Congressional Fellow Kathie E. Hanna
Churchton, Maryland
Charlotte Brown
Dwayne L. Smith
Word Processing Specialist
Research Assistant Judith Hellerstein
Northwestern University
Monica Finch
Jacqueline T. Keller
Word Processing Specialist
Research Analyst James H. Jorgensen
University of Texas
Louise Staley
CONTRIBUTING STAFF
Office Administrator
Karen Kaunitz
Beth Hadley
Jacksonville Baptist Medical
Carolyn Swann
Senior Analyst Center
PC Specialist
CONTRACTORS Calvin Kunin
Ohio State University
Michael J. Bennett
Washington, DC
David H. Persing
Mayo Clinic Rochester
Mitchell Burken
Philadelphia V.A. Hospital
David Relman
Stanford University
Julian Davies
The University of British Barbara Rosenkrantz
Columbia Harvard University
Susan Feinman Lee Sabath
Potomac, Maryland University of Minnesota
vi
C
ontents
1 Summary, Conclusions, Issues and Options 1
Summary 1
Origins of the Antibiotic Era 2
Survey of Antibiotic Resistance 3
Costs of Antibiotic-Resistant Bacterial Diseases 6
Reducing the Impacts of Antibiotic-Resistant Bacteria 8
Conclusions 18
Issues and Options for Prolonging Effectiveness of
Antibiotics 19
Issues and Options for Encouraging Development
of New Antibiotics 28
2 Introduction 33
The Discovery of Antibiotics 36
Confronting Antibiotic Resistance 45
References 46
3 Antibiotic Use and Resistance in the
Community 49
Introduction 49
Populations Susceptible to Antibiotic-Resistant
Bacteria 53
Factors in the Emergence of Bacterial Diseases 57
Changes in Disease Patterns 59
Surveillance of Antibiotic-Resistant Bacteria 61
Conclusions 63
References 65
4 Antibiotic Use in Hospitals 69
Infections Acquired in the Hospital 69
The Rise of Antibiotic-Resistant Infections in
Hospitals 71
The Uses of Antibiotics in Hospitals 73
Legal Aspects of Antibiotic Use 75
Controlling the Emergence and Spread of Antibiotic
Resistance in Hospitals 76
vii
Hospital Accreditation and Infection Control Regulations
Under Medicare 80
Costs of Controlling the Emergence and Spread of
Antibiotic-Resistant Bacteria 93
Conclusions 96
References 96
5 Antibiotic Development 101
Designing New Antibiotics 101
Antibiotics in Current Clinical Use 104
Antibiotics That Inhibit or Block DNA Replication or
Protein Synthesis 109
Development of New Antibiotics From Old 110
New Research Tools 113
Antibiotics From New Sources 113
Getting New Antibiotics to Market 118
Patents 120
Pricing of Drugs Developed in Part by Federal
Research 121
Conclusions 121
References 122
6 New Technologies for Infection Diagnosis and
Control 127
Diagnostic Methods 127
Vaccines 142
Stimulating the Immune System 146
Targeted Delivery of Antibiotics 146
Reducing Infections by Modifying Devices 147
Old Therapies 150
Summary 151
References 151
viii
7 Antibiotics in Animal Husbandry 155
Antibiotic Use in Food Production 158
Antibiotic-Resistant Bacteria in Humans 159
Controversy About Antibiotic Use in Raising
Livestock 162
Controversy Over Fluoroquinolones in Food
Production 164
References 165
Appendix A: Coverage of Antibiotic Resistance in
the Popular Literature, 1950 to 1994 167
Appendix B: Glossary 173
Appendix C: Acknowledgments 181
ix
Summary,
Conclusions,
Issues and
1
Options
SUMMARY zImpacts of Antibiotic-Resistant
A Bacteria:
s more and more bacteria become resis-
tant to the effects of antibiotics and as
n Difficult-to-treat infections: Many strains of
the flow of new antibiotics into medical
bacteria are resistant to one or more of the 100
practice slows, it is clear that the pro- antibiotics now in use. Physicians may have to
nouncement of the Surgeon General of the try a number of different antibiotics until one
United States nearly a quarter century ago that it proves effective.
was time to “close the book on infectious dis- n Untreatable infections: Some strains of bacte-
eases” was premature.1 Indeed, the popular press ria are resistant to all available antibiotics.
and some experts worry that we are headed Currently, infections caused by these bacteria
toward an era of infectious diseases akin to the are fairly uncommon, but they are rapidly
increasing. Additionally, other bacteria are
one that existed before antibiotics were intro-
resistant to all but one antibiotic, and they are
duced over a half-century ago.
expected to become resistant to all antibiotics.
This Office of Technology Assessment (OTA)
n Antibiotic use increases the spread of antibi-
report is a response to congressional requests
otic-resistant bacteria: Antibiotic use creates
(see box1-1) for a description of the threat posed
“selective pressure” that promotes the spread
by antibiotic-resistant bacteria to our society.
of resistant bacteria. Susceptible bacteria are
This report explores the biological bases for the
killed or inhibited, and resistant bacteria sur-
development of bacterial resistance to antibiot-
vive and multiply. As bacteria become resis-
ics, describes new antibiotics that are in research
tant to increasing numbers of antibiotics, the
and development, and outlines a number of strat- remaining effective antibiotics are used more
egies to control the proliferation of antibiotic- often—increasing the selection pressure for
resistant bacteria. bacteria to become resistant to them.
1 Citations to the literature are not included in this summary. Complete citations are included in other chapters.
| 1