Management of Infections Caused by Vancomycin-Resistant Gram-Positive Bacteria

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For 3 decades, vancomycin has been a favored therapy for serious penicillin- and cephalosporin-resistant Gram-positive bacterial infections. Development of vancomycin resistance may have been restrained by the requirement for intravenous administration, which limited its use and lessened exposure to the gastrointestinal flora. Nevertheless, physicians are increasingly encountering children and adults infected with vancomycin-resistant Gram-positive organisms. Resistance to vancomycin has been encountered in all commonly occurring, clinically significant Gram-positive bacterial species except Streptococcus pyogenes, Streptococcus pneumoniae, and Streptococcus agalactiae.1 Although therapeutic options are usually guided by the antimicrobial susceptibilities of individual isolates, recommended infection-control measures vary with the specific species and the mechanism of resistance.VANCOMYCIN-RESISTANT STAPHYLOCOCCUS AUREUSVancomycin-resistant Staphylococcus aureus (VRSA) were first recognized in Japan in 1996; the first case of infection due to VRSA in the United States was reported in 2002.2 Since then, at least 8 additional cases of VRSA infection have been identified in the United States, with more than half of these cases occurring in Michigan.3,4 Isolates often seem to have evolved independently in settings where patients were previously colonized with vancomycin-resistant enterococcus (VRE) and methicillin-resistant S. aureus (MRSA).4 Environments that promote biofilm formation may facilitate transmission of resistance from VRE to MRSA.4VRSA isolates (vancomycin MIC ≥16 μg/mL) are fundamentally different from vancomycin-intermediate S. aureus (VISA) isolates (vancomycin MIC = 4–8 μg/mL).2 Resistance in VISA isolates is typically mediated via mechanisms that develop in the presence of vancomycin and are not readily transferrable to other strains. The potential for spread of these isolates is low in the absence of vancomycin therapy. In contrast, VRSA isolates uniformly contain the vanA gene derived from enterococcus (discussed below). The VanA phenotype is transferable to other MRSA strains and across microbial species, with a much greater potential for spread, even in the absence of vancomycin therapy.2Thus far, VRSA outbreaks have not occurred; however, because of the potential for spread with dire consequences, a case of VRSA infection warrants a more rigorous infection-control response than a case of infection with MRSA, VISA, or VRE. Infection-control measures should be implemented urgently according to a written plan, if VRSA is suspected.2 The local health department and the Centers for Disease Control and Prevention should be consulted immediately. Management of contacts should occur according to contact categorization. Attempts to decolonize individuals who are found to be colonized should be considered on a case-by-case basis.Infections with S. aureus isolates that have vancomycin MICs ≥4 μg/mL typically do not respond clinically to vancomycin therapy.2 To date, all VRSA have also been found to be resistant to methicillin. Fortunately, all VRSA and VISA isolates have been susceptible to one or more commercially available antibiotics. Recommended antibiotics for VRSA and VISA, according to susceptibilities and other clinical considerations, are listed in Table 1.2,4 Secondary agents include teicoplanin (not available in the United States), trimethoprim-sulfamethoxazole, tetracycline, rifampin (usually in combination therapy), and chloramphenicol.VANCOMYCIN-RESISTANT ENTEROCOCCIVRE infection was first reported in 1988.5 Subsequently, infections with VRE in the United States have been observed primarily in large teaching hospitals.6,7 Not only are VRE found in all regions of the United States,8 but the rate of vancomycin resistance among enterococci isolated from patients in this country is higher than the rates in Canada, Western Europe, and Latin America,8 possibly related to the widespread use of vancomycin in the United States.

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