The Resistance Phenomenon in Microbes and Infectious Disease Vectors Implications for Human Health and Strategies for Containment: Workshop Summary (2003) / Chapter Skim
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Summary and Assessment
Summary and Assessment
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What is perhaps most notable today is the increasing degree to which microbial resistance has become an important health threat and the continuing failure of the nation, indeed the world, to mount an adequate response. Drug resistance is accumulating and accelerating, thereby reduc1In this report, antibiotics are defined as substances (not limited to those produced from microorganisms)
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Today, some pathogenic strains of bacteria that were previously readily amenable to antibiotic therapy have become resistant to all available antibiotics, while strains of many other serious pathogens are now resistant to all but one easily administered drug, placing them on the brink of being untreatable. Coupled with the unrelenting emergence of antimicrobial resistance among common pathogens, there is a growing sense that drug discovery efforts are yielding fewer and fewer truly new leads toward novel classes of antimicrobial agents.
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Drug-resistant microbes also are becoming more common in the community. At least five major bacterial pathogens,2 including Streptococcus pneumoniae, which remains a major worldwide cause of pneumonia, meningitis, sepsis, and otitis media, and Mycobacterium tuberculosis, which causes tuberculosis, have developed resistance to a number of drugs.
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For example, the World Health Organization (WHO) recently declared antimicrobial resistance to be one of the top issues in global health.
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Case Studies of Antimicrobial Resistance Workshop speakers presented updates on the genetics and ecology of several important pathogens. Among the microbes and infectious diseases discussed: The bacterial strains staphylococci, enterococci, and pneumococci are ancient evolutionary companions of humans.
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· Develop therapeutic interventions that target the "ecological reservoirs" of bacterial pathogens, particularly drug-resistant strains. Use drugs prudently in all patient care settings and in national and international disease-control programs, especially when a drug has not yet triggered widespread microbial resistance.
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Malaria control programs that already face complex challenges presented by multi-drug-resistant strains of the parasite are additionally undermined by mosquito populations that show increasing resistance to the pyrethroid-treated bed nets commonly used to reduce malaria transmission. Workshop participants agreed that scientists studying microbial resistance can learn much from the work of those studying these aspects of vector control, including how to prevent vectors from developing resistance to pesticides.
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Foster multidisciplinary research efforts involving scientists studying microbial resistance and those studying various aspects of vector control, including how to prevent vectors from developing resistance to pesticides. · Expand and apply knowledge of the basic molecular mechanisms underlying resistance to insecticides in order to develop novel control strategies that can truly manage resistance.
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Meanwhile, in many developing countries, antimicrobial agents are readily available and can be purchased as a commodity without the advice or prescription of a physician or other trained health care provider. In such settings, drugs are often of questionable quality, with less than full potency, thereby possibly promoting the emergence of resistant pathogenic organisms whether simply colonizers or in fact those involved in producing disease in people taking them.
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Enforce infection control measures among health care workers in acute and long-term care facilities, and other environments such as child care facilities. · Improve physicians' prescribing practices through such means as education, formulary restrictions, multidisciplinary drug utilization evaluation, and computerized decision support systems.
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The traditional means to overcoming resistance problems has been to extend the useful life of current classes of antimicrobial drugs, often by developing slightly different chemical derivatives, or to develop wholly new classes of drugs that are not yet subject to resistance. However, the first route often provides marginal gains at best.
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As part of the current regulatory approval process, drug developers must evaluate whether their candidate achieves a clinical cure; that is, whether a person receiving the agent becomes free of symptoms. But this marker of success may not correlate with the extent to which the drug killed and eliminated the pathogen.
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Workshop participants stressed that this response will require participation by individuals, organizations, and governments at the local, state, national, and international levels. The primary blueprint for federal actions in the United States is the Public Health Action Plan to Combat Antimicrobial Resistance, issued in
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The plan calls for increasing understanding of microbial physiology, ecology, genetics, and mechanisms of resistance; augmenting the existing research infrastructure to support a critical mass of researchers in antimicrobial resistance and related fields; and translating research into clinically useful products, such as novel approaches to detecting, preventing, and treating antimicrobial-resistant infections. Strategies include fostering product development to ensure that researchers and drug manufacturers are focused on current and projected gaps in the arsenal of antimicrobial drugs, vaccines, and diagnostics and of potential markets for these products; stimulating the development and appropriate use of products for which customary market incentives are inadequate; and optimizing the development and use of veterinary and related agricultural products that reduce the transfer of resistance to pathogens that can infect humans.
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The campaign centers around four basic strategies that clinicians can use to prevent antimicrobial resistance. These strategies include preventing infections so as to directly reduce the need for antimicrobial exposure and the emergence and selection of resistant strains; diagnosing and treating infections properly, which will benefit patients and decrease the opportunity for development and selection of resistant microbes; using antimicrobials wisely, since optimal use will ensure proper patient care while avoiding overuse of broad-spectrum antimicrobials and unnecessary treatment; and preventing transmission of resistant organisms from one person to another by emphasizing the importance of infection control.
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resistance: . Complete implementation of the Public Health Action Pan to Combat Antimicrobial Resistance.
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· Expand professional education and training, such as through expanded use of the CDC's "12 Steps to Prevent Antimicrobial Resistance" programs aimed primarily at front-line clinicians dealing with high-risk patients. Professional societies also can take a more active role in promoting education for their members.
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