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Institute of Medicine (US) Forum on Emerging Infections; Knobler SL, Lemon SM, Najafi M, et al., editors. The Resistance Phenomenon in Microbes and Infectious Disease Vectors: Implications for Human Health and Strategies for Containment: Workshop Summary. Washington (DC): National Academies Press (US); 2003.

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The Resistance Phenomenon in Microbes and Infectious Disease Vectors: Implications for Human Health and Strategies for Containment: Workshop Summary.

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Preface

The Forum on Emerging Infections was created in 1996 in response to a request from the Centers for Disease Control and Prevention and the National Institutes of Health. The goal of the Forum is to provide structured opportunities for representatives from academia, industry, professional and interest groups, and government1 to examine and discuss scientific and policy issues that are of shared interest and that are specifically related to research and prevention, detection, and management of emerging infectious diseases. In accomplishing this task, the Forum provides the opportunity to foster the exchange of information and ideas, identify areas in need of greater attention, clarify policy issues by enhancing knowledge and identifying points of agreement, and inform decision makers about science and policy issues. The Forum seeks to illuminate issues rather than resolve them directly; hence, it does not provide advice or recommendations on any specific policy initiative pending before any agency or organization. Its strengths are the diversity of its membership and the contributions of individual members expressed throughout the activities of the Forum.

ABOUT THE WORKSHOP

Resistance in microbes—bacterial, viral, or protozoan—to therapeutics is neither surprising nor new. It is, however, an increasing challenge as drug resistance accumulates and accelerates, even as the drugs for combating infections are reduced in power and number. Today some strains of bacterial and viral infections are treatable with only a single drug; some no longer have effective treatments. The disease burden from multi-drug-resistant strains of tuberculosis, malaria, hepatitis, and HIV is growing in both developed and developing countries.

Infections caused by resistant microbes may fail to respond to treatment, resulting in prolonged illness and greater risk of death. Treatment failures also lead to longer periods of infection, which increase the numbers of infected people moving into the community and thus expose the general population to the risk of contracting a resistant strain of infection. When infections become resistant to first-line antimicrobials,2 treatment has to be switched to second- or third-line drugs, which are nearly always much more expensive and sometimes more toxic as well. In many countries, the high cost of such replacement drugs is prohibitive, with the result that some diseases can no longer be treated in areas where resistance to first-line drugs is widespread. Most alarming of all are diseases where resistance is developing for virtually all currently available drugs. Even if the pharmaceutical industry were to step up efforts to develop new replacement drugs immediately, current trends suggest some diseases will have no effective therapies within the next ten years.

More recently, the challenges of resistance are compounded by growing concerns about the possible use of biological weapons leading to large-scale disease outbreak or exposure. The ability to respond effectively to such exposures could be significantly compromised by the introduction of drug-resistant pathogens. The use of prophylactic drugs or therapies on large populations may also contribute to the development of drug resistance and thus increase both the immediate and longer-term challenges of treating infectious diseases.

A number of trends in human behavior increasingly contribute to the emergence of resistance to antimicrobial agents. Host behaviors such as noncompliance with recommended treatment and self-medication are among the most complicit problems associated with the development of resistance. However, the duration of therapy for most acute infections has been determined empirically by treatment outcome, and more research is required on the effect of a reduction of treatment duration on the risk of the emergence of resistance. Other factors contributing to the rise in antimicrobial resistance include over-prescribing by physicians, failure to control the spread of infection in hospitals and long-term care facilities, and the overuse of antimicrobials in animals used for food products.

These trends are currently outpacing scientific discovery to counter resistant pathogens. However, one promising aspect of such factors in the emergence of resistance is their amenability to change, which may be accomplished through public education, appropriate training, political action, and domestic and international regulation.

Beyond the development of resistance in microbes, the ever-increasing resistance of disease vectors to biological and chemical pesticides looms as another complicating factor in efforts to control and eliminate the emergence of infectious diseases. Resistance to insecticides has appeared in the major insect vectors from every genus (e.g., mosquitoes, sand flies, ticks, fleas, and lice). Resistance has developed to every chemical class of insecticide, including microbial drugs and insect growth regulators. Insecticide resistance is predicted to have an increasing and profound effect on the reemergence of most vector-borne diseases. And where resistance has not contributed to disease emergence, it is expected to threaten disease control. Malaria control programs that already face complex challenges presented by multi-drug-resistant strains of the parasite are additionally undermined by vector mosquito populations that show increasing resistance to the pyrethroid-treated bed nets used to reduce malaria transmission.

Resistance is a natural response of microbes and other organisms to selective pressure from antimicrobial and other biological and chemical countermeasures. Adaptive mechanisms in the organisms permit survival and the development of genetic resistance. While the emergence of resistance cannot be eliminated, the rate and extent of its occurrence can be contained. In order to contain the threats posed to human health by resistance, it is important to determine the magnitude and trends of resistance and to define the relative importance of different contributing factors, such as therapeutic, behavioral, economic and social, and health systems factors, as well as veterinary and agricultural misuse. Based on this understanding it may be possible to develop effective methods to contain resistance in different settings.

Through invited presentations and participant discussion, the February 6–7, 2002, Forum workshop explored the causes and consequences of the resistance phenomenon. The Forum discussion also examined the scientific evidence supporting current and potential strategies for containment of resistance in microbes, vectors, and animal and human hosts. Additionally, the methods and measures of a response for industry, federal regulation, domestic and international public health, federal and academic research, and the private health care sector were debated.

ORGANIZATION OF WORKSHOP SUMMARY

This workshop summary report is prepared for the Forum membership in the name of the editors, with the assistance of staff and consultants, as a collection of individually authored papers. Sections of the workshop summary not specifically attributed to an individual reflect the views of the editors and not those of the Forum on Emerging Infections' sponsors or the Institute of Medicine (IOM). The contents of the unattributed sections are based on the presentations and discussions that took place during the workshop.

The workshop summary is organized within chapters as a topic-by-topic description of the presentations and discussions. Its purpose is to present lessons from relevant experience, delineate a range of pivotal issues and their respective problems, and put forth some potential responses as described by the workshop participants. The Summary and Assessment chapter discusses the core messages that emerged from the speakers' presentations and the ensuing discussions. Chapter 1 is an introduction and overview of the resistance phenomenon. Chapters 2 to 7 begin with overviews provided by the editors, followed by the edited presentations made by the invited speakers. Appendix A is an authored paper describing the consequences of antimicrobial use in agriculture. Appendix B presents the workshop agenda. Appendix C is a list of information resources on resistance. Appendixes D, E, and F contain the executive summaries of three government reports on the topic of antimicrobial resistance. Appendix G presents Forum member and speaker biographies.

Although this workshop summary provides an account of the individual presentations, it also reflects an important aspect of the Forum philosophy. The workshop functions as a dialogue among representatives from different sectors and presents their beliefs on which areas may merit further attention. However, the reader should be aware that the material presented here expresses the views and opinions of those participating in the workshop and not the deliberations of a formally constituted IOM study committee. These proceedings summarize only what participants stated in the workshop and are not intended to be an exhaustive exploration of the subject matter.

ACKNOWLEDGMENTS

The Forum on Emerging Infections and the IOM wish to express their warmest appreciation to the individuals and organizations who gave valuable time to provide information and advice to the Forum through participation in the workshop.

The Forum is indebted to the IOM staff who contributed during the course of the workshop and the production of this workshop summary. On behalf of the Forum, we gratefully acknowledge the efforts led by Stacey Knobler, director of the Forum, and Marjan Najafi, research associate, coeditors of this report, who dedicated much effort and time to developing this workshop's agenda, and for their thoughtful and insightful approach and skill in translating the workshop proceedings and discussion into this workshop summary. We would also like to thank the following IOM staff and consultants for their valuable contributions to this activity: Tom Burroughs, Laurie Spinelli, Judith Bale, Mark Smolinski, Katherine Oberholtzer, Patricia Cuff, Jennifer Otten, Clyde Behney, Bronwyn Schrecker, Sally Stanfield, Sally Groom, Michele de la Menardiere, and Beth Gyorgy.

Finally, the Forum also thanks sponsors that supported this activity. Financial support for this project was provided by the U.S. Department of Health and Human Services' National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration; U.S. Department of Defense; U.S. Department of State; U.S. Department of Veterans Affairs; U.S. Department of Agriculture; American Society for Microbiology; Burroughs Wellcome Fund; Eli Lilly & Company; Pfizer; GlaxoSmithKline; and Wyeth-Ayerst Laboratories. The views presented in this workshop summary are those of the editors and workshop participants and are not necessarily those of the funding organizations.

Adel Mahmoud, Chair

Stanley Lemon, Vice-Chair

Forum on Emerging Infections

Footnotes

1

Representatives of federal agencies serve in an ex officio capacity. An ex officio member of a group is one who is a member automatically by virtue of holding a particular office or membership in another body.

2

In this report, antibiotics are defined as substances (not limited to those produced from microorganisms) that can kill or inhibit the growth of bacteria, while antimicrobials are substances that destroy or inhibit the growth of pathogenic groups of microorganisms, including bacteria, viruses, protozoa, and fungi.

Copyright © 2003, National Academy of Sciences.
Bookshelf ID: NBK97136

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