Antibiotic resistance: synthesis of recommendations - libdoc.who.int

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WHO/CDS/CSR/DRS/2001.10
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WHO/CDS/CSR/DRS/2001.10
ORIGINAL: ENGLISH
DISTRIBUTION: GENERAL
Antibiotic resistance:
synthesis of
recommendations
by expert policy groups
Alliance for the Prudent Use of Antibiotics
JL Avorn, JF Barrett, PG Davey, SA McEwen,
TF O’Brien and SB Levy
Boston, MA, United States of America
World Health Organization OR
F
MENT TEGY
U A
C R F
O T O
A BACTKHGE ROWFUHONO RD GCLDOOANBNTATAILI MSNIECMSIRESONTTB AINALCE
R
Acknowledgements
The World Health Organization (WHO) and the Alliance for the Prudent use of Antibiotics (APUA)
acknowledge the United States Agency for International Development (USAID) for their concern about
the issue of antibiotic resistance and their support in producing this report.
Stuart B. Levy, President of APUA, ensured that the report was accurate and comprehensive and that it
would benefit both Ministers of Health and health care workers at the local level who can make a differ-
ence.
Kathleen Young, the Executive Director of APUA, recognized the contribution that APUA could make to
support WHO’s Global Strategy through this project. She designed the initial format and assured the
quality of the report.
Barbara Souder, the Project Director, coordinated all aspects of this report and Margaret Kruse, a scientist
and writer, acted as chief technical writer and production engineer.
APUA gratefully acknowledges the assistance of its support staff: Sarann Bielavitz, for summarizing the
reports by the expert policy groups; Brian Price for the graphics; Jennifer Mills-Knutsen for administrative
coordination; and Ellen Wells for bibliographic and editorial assistance.
Julia J. Chuang, from Scientific Information Resources, Bristol-Myers Squibb, United States, is gratefully
acknowledged for her research work on Chapter IV.
© World Health Organization 2001
This document is not a formal publication of the World Health Organization (WHO), and all rights are reserved by the Organiza-
tion. The document may, however, be freely reviewed, abstracted, reproduced and translated, in part or in whole, but not for sale or
for use in conjunction with commercial purposes.
The views expressed in documents by named authors are solely the responsibility of those authors.
The designations employed and the presentation of the material in this document, including tables and maps, do not imply the
expression of any opinion whatsoever on the part of the secretariat of the World Health Organization concerning the legal status of
any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on
maps represent approximate border lines for which there may not yet be full agreement.
The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by
WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary
products are distinguished by initial capital letters.
Designed by minimum graphics
Printed in Switzerland
WHO/CDS/CSR/DRS/2001.4 DRUG RESISTANC IN MALARIA
Contents
List of acronyms v
Executive Summary 1
Introduction Stuart B. Levy 11
Chapter I Improve and expand surveillance Thomas F. O’Brien 15
Chapter II Increase awareness: optimize patient and provider behaviour Jerry L. Avorn 33
Chapter III Strengthen sanitation, infection control, and regulatory measures Peter G. Davey 39
Chapter IV Encourage research and product development John F. Barrett 53
Chapter V Improve antibiotic use in animals Scott A. McEwen 65
Conclusion Stuart B. Levy 81
References 83
Some useful web sites 87
Appendix A Summaries of reports by expert policy groups (1987–2000) 89
Appendix B Local action around the world 125
Appendix C About the authors 153
iii

WHO/CDS/CSR/DRS/2001.10 ANTIBIOTIC RESISTANCE: SYNTHESIS OF RECOMMENDATIONS BY EXPERT POLICY GROUPS
List of acronyms
AHRQ Agency for Healthcare Research DTC Drug and Therapeutic Committee,
and Quality, United States Viet Nam
AIDS Acquired Immune Deficiency DVA Department of Veterans’ Affairs,
Syndrome United States
AIEPI Integrated Management of Child- EARS European Antimicrobial Resistance
hood Diseases, Pan American Surveillance
Health Organization EMEA European Medicines Evaluation
APO Audit Project Odense Agency
AR antimicrobial/antibiotic resistance ENT ear, nose, and throat
ARM antimicrobial resistance manage- EPA Environmental Protection Agency,
ment/manager/monitor United States
ASM American Society for Microbiology ESBIC European Society for Biomodu-
BBSRC Biotechnology and Biological lation and Chemotherapy
Sciences Research Council, United ESCMID The European Society for Clinical
Kingdom Microbiology and Infectious
BSAC British Society for Antimicrobial Diseases
Chemotherapy EU European Union
CA-SFM Comite de l’Antibiogramme de la FDA Food and Drug Administration,
Société Française de Microbiologie, United States
France FESCI Federation of the European
CDC Centers for Disease Control and Societies for Chemotherapy
Prevention, United States GAARD Global Advisory on Antibiotic
CEM/NET Centro de Epidemiologia Molecu- Resistance Data
lar, Portugal/Network for Epide- GAO General Accounting Office,
miological Tracking of Antibiotic United States
Resistant Pathogens, United States GPs General Practitioners
CISET Committee on International HACCP Hazard Analysis, Critical Control
Science Engineering and Technol- Point, United Kingdom
ogy, United States HCFA Health Care Financing Adminis-
CMO Chief Medical Officer tration, United States
CNS central nervous system HELICS Hospitals in Europe Link for
CPD continuing professional develop- Infection Control through Surveil-
ment, United Kingdom lance
DANMAP Danish Integrated Antimicrobial HGOH Hospital Gynecology-Obstetric
Resistance Monitoring and Hanoi, Viet Nam
Research Program HIV Human Immunodeficiency Virus
DDA Department of Drug Administra- HMG His/Her Majesty’s Government
tion, Nepal HMO Health Maintenance Organization,
DDD defined daily dose United States
DHHS Department of Health and Human HRSA Health Resources and Services
Services, United States Administration, Department of
DoD Department of Defense, United Health and Human Services,
States United States
v
ANTIBIOTIC RESISTANCE: SYNTHESIS OF RECOMMENDATIONS BY EXPERT POLICY GROUPS WHO/CDS/CSR/DRS/2001.10
ICARE Intensive Care Antimicrobial NNISS National Nosocomial Infections
Epidemiology, Centers for Disease Surveillance System
Control and Prevention, United OIE Office International des Epizooties
States OTA Office of Technology Assessment,
ICU intensive care unit United States Congress
ID infectious disease OTC over the counter
IDSA Infectious Diseases Society of PAHO Pan American Health Organiza-
America tion
IMF International Monetary Fund PCR polymerase chain reaction
IND investigational new drug PHCP/GTZ Primary Health Care Project/
IOM Institute of Medicine, United Deutsche Gessellschaft für
States Technische Zusammenarbeit
ISC International Society of Chemo- PHLS Public Health Laboratory Service,
therapy England and Wales
KOL key-opinion-leader PHON Pharmaceutical Horizon of Nepal
MDRTB multidrug-resistant tuberculosis PRP penicillin-resistant pneumonia
MIC minimal inhibitory concentration, PRSP penicillin-resistant Streptococcus
testing method pneumoniae
MRC Medical Research Council, QC quality control
England RCCDC Regional Center of Communicable
MRSA methicillin-resistant Staphylococcus Disease Control, Malmo, Sweden
aureus R&D research and development
MSH Management Sciences for Health, RTI respiratory tract infection
Boston, United States SIGN Scottish Intercollegiate Guideline
NAO National Audit Office, United Network
Kingdom SMA Scottish Microbiology Association
NARMS National Antimicrobial Resistance SMAC Standing Medical Advisory
Monitoring System, United States Committee, United Kingdom
NATAC National Antibiotic Therapeutic SRH Smolensk Regional Hospital,
Advisory Committee, Nepal Russia
NCCLS National Committee for Clinical STD sexually transmitted disease
and Laboratory Standards, Europe STRAMA Swedish Strategic Program for the
NEPI Network for Rational Use of Antimicrobial
Pharmacoepidemiology, Sweden Agents and Surveillance of
NHS National Health Service, United Resistance
Kingdom TB tuberculosis
NIAID National Institute of Allergy and TIGR The Institute for Genomic
Infectious Diseases, United States Research, Maryland, United States
NIBSC National Institute for Biological TSN The Surveillance Network,
Standards and Control, United California and Virginia, United
Kingdom States
NICE National Institute for Clinical USAID United States Agency for Interna-
Excellence, Great Britain tional Development
NICE Nosocomial Infection Control in USDA Department of Agriculture, United
Europe States
NIH National Institutes of Health, UTI urinary tract infection
United States VRE vancomycin-resistant enterococci
NINSS Nosocomial Infection National WB World Bank
Surveillance Scheme WHO World Health Organization
NISS Nosocomial Infection Surveillance WMA Welsh Microbiological Association
System WP Working Party
NME new molecular entity WTO World Trade Organization
NSG National Steering Group
vi
WHO/CDS/CSR/DRS/2001.10 ANTIBIOTIC RESISTANCE: SYNTHESIS OF RECOMMENDATIONS BY EXPERT POLICY GROUPS
Executive Summary
In the not too distant past, antibiotics could be APUA also collected information from their in-
counted on to treat a bacterial infection. Those days ternational chapters about experiences at the local
are almost gone, as bacteria have emerged that are level; these reports, reflecting the views of APUA
resistant to each of the antibiotics currently on the Chapters and not necessarily reflecting national
market. Deaths have occurred as a result of untreat- policy, are included in Appendix B.
able bacterial infections. This trend is expected to After review, analysis and update, and with ad-
continue unless the problem of antibiotic resist- ditional insights from the authors of the individual
ance can be curbed. In response to this threat, the chapters of this review, the key recommendations
World Health Organization (WHO) has worked emanating from the 25 expert reports are summa-
with many partners, including the Alliance for the rized below under the following headings:
Prudent Use of Antibiotics (APUA), to develop the
• Increase awareness of the antibiotic resistance
WHO Global Strategy for Containment of Anti-
problem
microbial Resistance (26).
As part of the development process of the WHO • Improve surveillance of antibiotic resistance
Global Strategy, WHO commissioned a series of
• Improve antibiotic use in people
technical reviews. APUA responded to WHO’s
• Regulate antibiotic use in animals
request to review reports on antibiotic resistance
prepared by prestigious scientific and governmen- • Encourage new product development
tal organizations over the last two decades. The pur-
• Increase resources to curb antibiotic resist-
pose of this review is to identify areas of consensus
ance in the developing world
in the experts’ recommendations in the selected
reports, update the findings, consider the barriers • Increase funding for surveillance, research and
to concerted action and suggest ways to move from education.
recommendations to action.
Under each heading recommendations have
Twenty-five expert reports (1–25—see Table 1,
been organized on the basis of the suggested level
Table 3 and Appendix A) compiled by scientific
of decision-making necessary for implementation
and medical authorities were selected for this re-
of the intervention i.e., “who can do what”.
view by APUA because they are highly referenced
A more detailed analysis of these recommenda-
in the literature and reflect extensive deliberations
tions is provided by the author of each chapter.
by a wide variety of key expert policy groups. In
developing this synthesis, APUA consulted five
Increase awareness of the antibiotic
medical and scientific experts on antibiotic resist-
resistance problem
ance who reviewed relevant sections of the reports.
Their reviews are presented in Chapters I–V and For real reforms in the use of antibiotics to occur,
cover the major areas of intervention, i.e., surveil- individuals in the general public and in public
lance, education of patient and provider behaviour, health and provider groups at the international,
prevention (including sanitary and infection con- national, and local levels must take ownership of
trol), research and product development, and anti- the problem and provide leadership to reverse this
biotic use in animals. Each author focused on those public health crisis.
reports with extensive subject matter related to their
area of investigation. In addition to summarizing
International organizations
findings from the expert policy reports, updated
information, references and authors’ insights were • Obtain worldwide commitments to establish
added. prudent antibiotic use policies.
1
ANTIBIOTIC RESISTANCE: SYNTHESIS OF RECOMMENDATIONS BY EXPERT POLICY GROUPS WHO/CDS/CSR/DRS/2001.10
National and municipal organizations Health care workers
• Publicize the outcomes of programmes from other • Educate the general public:
countries: Communicate global trends in antibi-
— Physicians: Discuss proper antibiotic use
otic resistance with potential local impact, such
with all patients.
as the results of the European Union’s legisla-
— Veterinarians: Discuss ways to minimize an-
tion against use of antibiotics in growth promo-
tibiotic use with animal owners, such as im-
tion. Collect and publicize the economic
proved farm hygiene and alternatives to
consequences, or lack thereof, of Denmark and
antibiotics as growth promoters.
Sweden’s complete ban on growth promoters.
• Educate the general public: The United Kingdom’s Improve surveillance of antibiotic
campaign to “cherish and conserve your natural resistance
flora” pointed out the beneficial aspects of bac-
The urgent recommendation for surveillance of
teria which can be obliterated by excessive anti-
antimicrobial resistance and plans for performing
biotic use. A campaign about proper antibiotic
surveillance have been elaborated upon over the past
use should be aimed at young children, the
two decades. Over that same period a succession of
parents of young children, workers in day care
unexpected, new and life-threatening resistance
centres, schoolteachers, those who work in agri-
problems have emerged and spread throughout the
culture, and policy-makers in all areas.
world. These global outbreaks have had little
• Promote communication: Facilitate communication
monitoring to support their ultimately failed con-
among academic institutions, government agen-
tainment. Only inadequate and fragmentary
cies, those who pay for health care, and pharma-
surveillance systems exist today.
ceutical manufacturers to reduce the extent to
which such groups act at cross purposes in rela-
National and municipal organizations
tion to antibiotic use and infection control.
Provide materials to support intervention pro- • Coordinate local surveillance networks: Public health
grammes and utilize communication tools such departments can take the initiative to contact
as the media and the Internet. medical centres and develop a surveillance net-
work. If an existing privately-initiated network
• Evaluate the curricula of universities: Undergraduate,
exists, the public health department should sup-
postgraduate and continuing education pro-
port and help that network to grow.
grammes at veterinary, medical, pharmacy, and
nursing schools should be evaluated to ensure • Recruit leaders for surveillance networks: The public
that prudent antimicrobial use and resistance are health department cannot pay for all the par-
given high priority. Courses should make ticipants that a surveillance network requires. It
students more aware of how to evaluate promo- has to find leaders within the network and use
tional materials and what questions to ask dur- their help to motivate all the participants to work
ing a sales presentation. together on the surveillance network.
• Support a reference laboratory: The public health
Health care institutions department should support a reference labora-
tory, hitherto lacking in many surveillance net-
• Use effective teaching methods for educating pre-
works. The network initiator’s laboratory may
scribers:
become the reference laboratory. With proper sup-
— Use group problem-solving sessions, role port, the reference laboratory can appreciably im-
playing, lectures. prove the performance of the network’s laboratories
— Focus on clinical issues one at a time. and connect, integrate, and interpret their data.
— Use an educational outreach worker for train-
• Share results of surveillance with international organi-
ing at the office.
zations.
— Use opinion leaders or district-level staff as
trainers. • Monitor resistance in food animals: Undertake regu-
—Repeat sessions to reinforce message. lar monitoring for resistant bacterial pathogens
— Apply community-based case management and commensals in food-producing animal
interventions. populations and animal-based food products.
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WHO/CDS/CSR/DRS/2001.10 ANTIBIOTIC RESISTANCE: SYNTHESIS OF RECOMMENDATIONS BY EXPERT POLICY GROUPS
• Monitor sentinel human populations: Evaluate the ers and detractors; how to reach goals, and
usefulness of monitoring sentinel human ways to build on existing audit systems.
populations (e.g. farm and abattoir workers) and
• Update guidelines based on surveillance data: Regu-
people in the community for infection and/or
larly update guidelines for antimicrobial use
colonization with resistant bacteria.
based on resistance surveillance data.
• Eliminate financial incentives that promote the misuse
Health care institutions
of antibiotics: In countries where governments
• Develop local surveillance networks: Medical centres subsidize the purchase of antimicrobial drugs,
can support data gathering within their centre legislative or regulatory changes in these subsi-
and join or start a local surveillance network. dies could lead to a decline in the use of the
drugs. Governments could investigate the effect
• Maintain a laboratory with adequate quality assurance
of changes in reimbursement on the prudent use
and trained technicians.
of antibiotics and on surveillance of prescribing
or resistance; for example, the United States
Health care workers
Congress Office of Technology Assessment
• Initiate a local surveillance network: A microbiologist (OTA) identified a potential problem with Med-
or infectious disease specialist can initiate an icaid and Medicare reimbursement policies.
antimicrobial resistance surveillance network;
• Monitor advertising: Develop and enforce ethical
most of the networks started in various coun-
standards concerning advertising of antibiotics
tries began in this way. The leadership and in-
to the general public to counteract the strong
terest of these individuals and their colleagues
commercial pressures from manufacturers to in-
can keep these networks functioning.
crease utilization of antibiotics and antibacterials.
• Consider the impact of new drugs on resistance during
Pharmaceutical companies
the drug approval process: Consideration of resist-
• Undertake post-marketing surveillance to detect emer- ance issues should be required prior to drug
gence of resistance to new antibiotics. approval for human, animal, or plant use.
• Support surveillance networks: Support the work of • Limit general access to new drugs.
a local surveillance centre through funding and/
• Establish post-marketing surveillance accords with
or surveillance projects.
producers to ensure early detection of emerging
resistance to new drugs.
Improve antibiotic use in people
National and municipal organizations Health care institutions
• Enforce the prudent use of antibiotics: For example, • Establish an Infection Control Committee for surveil-
the United States federal government could lance of infection; identification of outbreaks;
adopt a strategy making the implementation of implementation of effective control measures
state policies to curb the misuse of antimicro- (e.g., hand washing); sterilization and disinfec-
bial drugs mandatory before states could receive tion of equipment and supplies.
federal funds earmarked for public health.
• Establish a Drugs and Therapeutics Committee to evalu-
• Create national and regional guidelines: National ate antibiotic use data, resistance patterns,
standards and guidelines should be created for efficacy and cost; make recommendations for
community infection control management with proper antibiotic use that are appropriate to a
the following features: particular clinical setting and population.
— A requirement that every district health
• Establish guidelines for appropriate antibiotic use: For
authority should have at least one commu-
maximum benefit, such guidelines should be:
nity infection control nurse.
— The ability to be adapted at the local level. — Based on evidence.
— An implementation protocol that includes — Relevant and appropriate to the clinical and
who is being targeted; how to stage the im- microbiological issues of a given population.
plementation; how to manage the support- — Developed with the involvement of the prac-
3