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Technology Assessment Board of the 103d Congress*
EDWARD M. KENNEDY, Massachusetts, Chairman
DON SUNDQUIST, Tennessee, Vice Chairman
SENATE HOUSE
ERNEST F. HOLLINGS, South Carolina GEORGE E. BROWN, JR., California
CLAIBORNE PELL, Rhode Island JOHN D. DINGELL, Michigan
ORRIN G. HATCH, Utah JIM McDERMOTT, Washington
CHARLES E. GRASSLEY, Iowa AMO HOUGHTON, New York
DAVE DURENBERGER, Minnesota MICHAEL G. OXLEY, Ohio
ROGER HERDMAN
C.
(Nonvoting)
Technology Assessment Advisory Council
JAMES C. HUNT, Chairman JOSHUA LEDERBERG
Distinguished Professor, Health Sciences Center Professor, Rockefeller University
University of Tennessee New York, New York
Memphis, Tennessee
DANIEL MULHOLLAN
MAX LENNON, Vice Chairman Director, Congressional Research Service
President and CEO The Library ofCongress
Washington, D.C.
Eastern Foods, Inc.
Atlanta, Georgia
THOMAS PERKINS
J.
CHARLES BOWSHER General Partner
A.
Comptroller General of the United States Kleiner, Perkins, Caufield and Byers
Washington, D.C. San Francisco, California
LEWIS M. BRANSCOMB JOHN F.M. SIMS
Director, Science, Technology & Public Vice President, Marketing
Policy Program, Harvard University Usibelli Coal Mine, Inc.
Cambridge, Massachusetts Fairbanks, Alaska
HERBERT (TED) DOAN L. DOUGLAS SMOOT
President (Ret.), The Dow Chemical Company Dean, College of Engineering & Technology
Midland, Michigan Brigham Young University
Salt Lake City, Utah
NEIL E. HARL
MARINA v.N. WHITMAN
Charles F. Curtiss Distinguished Professor
Iowa State University Professor, Institute of Public Policy Studies
Ames, Iowa University of Michigan
Ann Arbor, Michigan
*TheTABforthe 104thCongresshasnotyetbeenappointed.
TheTechnologyAssessmentBoardapprovesthereleaseofthisreport.Theviewsexpressedinthisreport
arenotnecessarilythoseoftheBoard,OTAAdvisoryCouncil,orindividualmembersthereof.
national
996
CENTER DR.
20892-1150
(MTIBIOTIORCSISTflllT
BACTERIA
Office of Technology Assessment
Congress of the United States
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).
ForsalebytheU.S.GovernmentPrintingOffice
SuperintendentofDocuments,MailStop:SSOP,Washington,DC 20402-9328
ISBN 0-16-048338-7
Penicillin, 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 ofthe assessment rests with OTA.
ROGER HERDMAN
C.
Director
Advisory
Panel
Gail Cassell, Ph.D. Prabhavathi B. Fernandes, Stuart Levy, M.D.
Professorand Chairman Ph.D. Professor ofMedicine and of
Department ofMicrobiology Vice President, Drug Molecular Biology and
University ofAlabama at Discovery Microbiology
Birmingham/University BiomolecularScreening Tufts University Medical
Station Bristol-Myers Squibb School
Birmingham, AL 35294 PO Box 4000 136 Harrison Ave.
MA
Princeton, NJ 08543-4000 Boston, 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-Chiefand
S-17136 Solna 2041 Georgia Ave., NW, Chairman
Sweden Room 5C-43 New England Deaconess
Washington, DC 20060 Hospital
Robert J. Bywater, Ph.D. DepartmentofMedicine/Room
Director, Anti-Infective Joshua Lederberg, Ph.D. 6A
Assessment Professor 110 Francis Street
MA
SmithKline Beecham Animal The Rockefeller University Boston, 02215-5553
Health New York, NY 10021-6399
Walton Oaks Barbara Murray, M.D.
Dorking Road Stephen Lerner, M.D. Professor ofMedicine and of
Tadworth Professor ofMedicine Microbiology and Molecular
Surrey KT20 7NT Wayne State University School Genetics
UK
ofMedicine Infectious Diseases
Harper Hospital/Division of University ofTexas 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. AlexanderTomasz, Ph.D. Craig Townsend, Ph.D.
Medical Director ProfessorandHead/Laboratory Chairman, Department of
Microbiology Laboratory ofMicrobiology Chemistry
Brigham and Women's The Rockefeller University The Johns Hopkins University
Hospital 230 York Ave., Box 52 Charles and 34th Streets
1 1
75 Francis Street New York, NY 10021-6399 Baltimore, MD 21218
MA
Boston, 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 ofInternal 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
NY
Albany, 12201-2002
V
p
roject Staff
Clyde J. Behney PRIMARY STAFF David Frankel
OTA
Assistant Director, 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
Word Processing Specialist Jacqueline T. Keller
Research Analyst James H. Jorgensen
University ofTexas
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 Reiman
Stanford University
Julian Davies
The University ofBritish Barbara Rosenkrantz
Columbia Harvard University
Susan Feinman Lee Sabath
Potomac, Maryland University ofMinnesota
VI
ontents
1 Summary, Conclusions, Issues and Options 1
Summary
1
Origins ofthe Antibiotic Era 2
Survey ofAntibiotic Resistance 3
Costs ofAntibiotic-Resistant Bacterial Diseases 6
Reducing the Impacts ofAntibiotic-Resistant Bacteria 8
Conclusions 18
Issues and Options for Prolonging Effectiveness of
Antibiotics 19
Issues and Options for Encouraging Development
ofNew Antibiotics 28
2 Introduction 33
The Discovery ofAntibiotics 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 ofBacterial Diseases 57
Changes in Disease Patterns 59
Surveillance ofAntibiotic-Resistant Bacteria 61
Conclusions 63
References 65
4 Antibiotic Use in Hospitals 69
Infections Acquired in the Hospital 69
The Rise ofAntibiotic-Resistant Infections in
Hospitals 71
The Uses ofAntibiotics in Hospitals 73
Legal Aspects ofAntibiotic Use 75
Controlling the Emergence and Spread ofAntibiotic
Resistance in Hospitals 76
vii
Hospital Accreditation and Infection Control Regulations
UnderMedicare 80
Costs ofControlling 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
DNA
Antibiotics That Inhibit or Block Replication or
Protein Synthesis 109
Development ofNew Antibiotics From Old 110
New Research Tools 113
Antibiotics From New Sources 113
Getting New Antibiotics to Market 118
Patents 120
Pricing ofDrugs 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 ofAntibiotics 146
Reducing Infections by Modifying Devices 147
Old Therapies 150
Summary 151
References 151
viii
