Global Epidemiology of Antimicrobial Resistance
Resistance to antimicrobial agents among clinically important pathogens in the community and hospital settings has compromised therapy and requires constant monitoring of emerging patterns. Although local information indexed by hospital service or ward remains preferred, the initiation of several comprehensive surveillance programs (SENTRY Antimicrobial Surveillance Program, MYSTIC Programme, ICARE, EARSS, etc.) offers quality susceptibility testing results to guide empirical treatment regimens. Enterococci and staphylococci with novel resistance mechanisms to glycopeptides (vancomycin, teicoplanin) require greater use of quinupristin/dalfopristin and linezolid. For streptococci, recent modifications of laboratory interpretive criteria for cefotaxime, ceftriaxone, and cefepime indicates that coverage remains at ≥ 95%. Extended-spectrum beta-lactamases in Enterobacteriaceae and multidrug resistance in Acinetobacter spp. and Pseudomonas aeruginosa most challenge our choices of effective agents for nosocomial infections. Few new drugs have surfaced for therapy of these gram-negative bacilli, and two- or three-agent combination regimens may be required with greater frequency, especially to cover the more prevalent resistances among both gram-positive cocci and gram-negative nonfermentative rods.

Objectives: Upon completion of this article, the reader should be able to: (1) list the most important resistance problems compromising the antibiotic treatment of infections caused by enterococci, staphylococci, and streptococci; (2) recognize the widest-spectrum agents capable of therapy for the most frequently isolated pathogens in the hospital environment; and (3) select two- or three-drug combination empirical regimens that would assure > 90% susceptibility of the suspected infection-producing isolates.
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Antimicrobial resistance continues to evolve and presents serious challenges in the therapy of both nosocomial and community-acquired infections. Previous reviews on this topic have cited that 50 to 60% of the more than 2 million nosocomial infections in the United States each year are caused by antimicrobial-resistant bacteria. Furthermore, the associated health care costs as well as morbidity and mortality have markedly increased. Statistics from the U.S. Department of Health and Human Services show that nosocomial infections contribute to more than 77,000 deaths/ year and cost the health care systems $5 to $30 billion. Recent structured studies that track the outcomes of "inadequately treated (organisms resistant to selected therapeutic antimicrobials)" patients with bloodstream infections (BSIs) documented greater hospital mortality compared with adequately treated counterparts. These studies emphasize the problem of resistance and urge the selection of appropriate broad-spectrum empirical regimens guided by the knowledge of pathogen occurrences and local/regional/global resistance patterns. Such practices require quality interactions with clinical microbiology laboratories and hospital pharmacies.

Although surveillance of organism prevalence and antibiograms should be performed on a local level, data on patient unit populations, specific care units, and infection or specimen type have not been widely available to the hospital medical staff. Therefore, surveillance networks have emerged to monitor various aspects of medical practice related to infection therapy and to address the problem of antimicrobial resistance. As stated by Bax et al, "no ideal surveillance system" exists, but some systems may provide meaningful results that can guide empirical antimicrobial regimens and minimize the consequences of antimicrobial resistance. These systems need to be integrated with continuing basic research into the discovery of new antimicrobial agents or vaccines, and be associated with educational programs for the prescribers (physicians and veterinarians) and the public. These systems, such as the Alexander Project or Network, EARSS, ICARE (CDC-NNIS), MYSTIC Programme, PROTEKT, SENTRY Antimicrobial Surveillance Program, and TSN, have been established by the pharmaceutical industry or by governmental agencies to monitor patterns of microbial resistance. A method to evaluate the utility of each system has been proposed, and the most comprehensive programs using reference, quantitative test methods, and interpretations appear to be the MYSTIC and SENTRY programs.

The MYSTIC Programme and the SENTRY Program were initiated in 1997, and each system contains approximately 100 active sentinel sites located in > 30 nations around the world. To assess the trends of resistance for the most important pathogens effecting nosocomial infection chemotherapy or those infections requiring hospitalization, the SENTRY Program results were summarized for pathogen prevalence by site of infection or hospital unit [BSIs, patients hospitalized with pneumonia, skin and soft tissue infections (SSTIs), urinary tract infections (UTIs), and intensive care units (ICUs)] and for the antimicrobial susceptibility patterns of 30 to 50 regularly tested agents. The results were further categorized by year (1997-2001) and by the geographic region [North America (Canada and United States), Latin America, and Europe]. Although medical centers in the Asia-Western Pacific region participated in the ongoing study, their results are not presented here.