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• W4253448825 abstract "The discovery and development of antimicrobial agents for clinical use was one of the crown jewels of medical progress in the 20th century. Unfortunately, the initial promise of these miracle drugs was soon set back to some degree by the emergence of resistance to these agents among a broad variety of bacterial species. It took <1 year for resistance to penicillin to develop; in fact, the first description of penicillinase occurred 1 year before penicillin was ever used clinically. However, the timeline for development of resistance to a particular antimicrobial agent varies among different bacterial species. For example, it took approximately 2 years after the deployment of methicillin for clinical resistance to develop in Staphylococcus aureus, but for vancomycin, it took >35 years. Although there are a few rare exceptions, such as group A streptococci that have not yet developed resistance to penicillin, resistance is an almost inevitable outcome of antimicrobial agent use. When penicillin was first used clinically in 1940, virtually all strains of S aureus worldwide were susceptible to penicillin. By 1947 almost 66%, and by 1951 75%, of S aureus from patients at the Boston City Hospital had become resistant to penicillin, although outpatient isolates remained susceptible.1Finland M. Emergence of antibiotic resistance in hospitals, 1935-1975.Rev Infect Dis. 1979; 1: 4-22Crossref PubMed Scopus (93) Google Scholar In fact, when I was a house officer in Boston in the 1960s, we prescribed penicillin for select patients who came into the hospital with outpatient-acquired staphylococcal infections; by 1967, however, it became clear that there was no difference in susceptibilities among inpatient and outpatient isolates.2Murray B.E. Moellering Jr, R.C. Patterns and mechanisms of antibiotic resistance.Med Clin North Am. 1978; 62: 899-923PubMed Google Scholar Currently, >90% of staphylococci worldwide are considered penicillin resistant. In 1959, methicillin, the first of the new antistaphylococcal penicillins, was launched clinically; 2 years later, descriptions of methicillin-resistant S aureus began to be published,3Parker M.T. Jevons M.P. A survey of methicillin resistance in Staphylococcus aureus.Postgrad Med J. 1964; 40: 170-178Crossref PubMed Scopus (39) Google Scholar albeit with a mechanism quite different from that of resistance to penicillin.4Chambers H.F. Methicillin resistance in staphylococci molecular and biochemical basis and clinical implications.Clin Microbiol Rev. 1997; 10: 781-791Crossref PubMed Google Scholar Nonetheless, the net result was the same: potential for therapeutic failure due to resistance. What drives antimicrobial resistance? The basic principle is selection of resistant organisms as a consequence of clinical and other uses of antibiotics. For example, the therapeutic use of antimicrobials in hospitals (especially in intensive care units) and in nursing homes clearly drives resistance by providing strong selective pressure for the emergence of resistant organisms. Therapeutic use of antimicrobials in outpatients and prophylactic use of these drugs also play a key driving role. These are all areas in which physicians may have a major impact on the course of antimicrobial resistance. Antimicrobial agents are also used extensively for veterinary purposes, as growth promoters, and to treat infections among agricultural and aquacultural animals. There also is industrial use of antimicrobials. Moreover, because many, if not most, antibiotic agents are natural products, there is even selection of resistant organisms in nature. What are the consequences of antimicrobial resistance? Therapeutic failure that may result in patient death from resistant infection is by far the costliest and most severe consequence of resistance. Clinicians also tend to use more and more antimicrobial agents to cover the possibility that they may be dealing with resistant organisms, especially in the intensive care unit among critically ill patients, adding substantially to the cost of patient care. There is a continuing need to develop new antimicrobials as well as reliable and practical susceptibility testing. In the initial decades, resistance challenge was met by the development of new antimicrobial agents. In recent years, the pharmaceutical pipeline has become less and less productive, so that we find ourselves in a peculiar and perplexing situation at the beginning of the 21st century. Bacteria are becoming more and more resistant to antimicrobial agents while our ability to identify new agents to cope with these resistant bacteria is diminishing. Therefore, we have to examine thoroughly the issue of antimicrobial resistance and the clinical problems it poses for both physicians and patients. The intent of this supplement to The American Journal of Medicine is to review the current evidence relating to the mechanisms and clinical outcomes of antimicrobial resistance, as well as to evaluate current clinical practices in light of available evidence to optimize clinical outcomes. The articles in this supplement aim to remind clinicians of the inherent complexities of antimicrobial resistance while providing a better understanding of its mechanisms, epidemiology, and management and suggesting the most effective tools to alter its course. The supplement begins with an article by Dr. Fred C. Tenover, who offers an overview of the mechanisms of resistance and discusses some of the major classes of bacteria. This is followed by articles by Dr. Louis B. Rice, who presents a review of gram-positive bacteria, with a special emphasis on methicillin-resistant S aureus, and by Dr. David L. Paterson, who covers gram-negative bacteria. Dr. John E. McGowan, Jr. then focuses on the nonfermenters. Pharmacokinetic and pharmacodynamic parameters that are important in driving and preventing resistance are discussed by Dr. Michael J. Rybak. Next, Dr. David K. Henderson reviews hospital infection control measures and practice recommendations. This is followed by Dr. Neil Fishman’s consideration of antimicrobial stewardship as it relates to the emergence, persistence, and prevention of antimicrobial resistance. This educational offering concludes with a summary of roundtable faculty discussions that, in addition to elaborating on frequently asked questions, also brings forth the views of infectious disease thought leaders and clinicians dedicated to the study of resistance." @default.
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• W4253448825 date "2006-06-01" @default.
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• W4253448825 title "Introduction" @default.
• W4253448825 doi "https://doi.org/10.1016/j.amjmed.2006.03.010" @default.
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