Nosocomial infection or colonization due to enterococci with high-level resistance to vancomycin (minimal inhibitory concentrations [MICs] between 64 and greater than 2000 mg/L) has occurred in 41 patients with renal disease. These vancomycin-resistant enterococci were cultured from many sources including blood. All but one strain contained one or more plasmids ranging in molecular weight from 1.0 to 40 Megadaltons (MDa). Vancomycin resistance was transferable by conjugation to a susceptible recipient strain of Enterococcus faecalis but this was not always associated with plasmid DNA. The emergence of transferable high-level vancomycin resistance in enterococci causing significant clinical infections is of particular importance since vancomycin is widely regarded as a reserve drug for the management of infections with multi-resistant Gram-positive organisms.
Vancomycin and teicoplanin are glycopeptides active against a wide range of gram-positive bacteria. For 30 years following the discovery of vancomycin in 1956, vancomycin resistance was not detected among normally susceptible bacteria recovered from human specimens. Since 1986, however, bacteria resistant to vancomycin or teicoplanin or both have been described. Strains of the genera Leuconostoc, Lactobacillus, Pediococcus, and Erysipelothrix seem inherently resistant to glycopeptides. Species and strains of enterococci and coagulase-negative staphylococci appear to have acquired or developed resistance. There are at least two categories of glycopeptide resistance among enterococci, characterized by either high-level resistance to vancomycin (MIC, greater than or equal to 64 mg/liter) and teicoplanin (MIC, greater than or equal to 8 mg/liter) or lower-level vancomycin resistance (MIC, 32 to 64 mg/liter) and teicoplanin susceptibility (MIC, less than or equal to 1 mg/liter). The two categories appear to have similar resistance mechanisms, although genetic and biochemical studies indicate that they have arisen independently. Among coagulase-negative staphylococci, strains for which vancomycin MICs are up to 20 mg/liter or teicoplanin MICs are 16 to 32 mg/liter have been reported, but cross-resistance between these glycopeptides varies. The selective advantage accorded to glycopeptide-resistant bacteria and the observation that high-level resistance in enterococci is transferable suggest that such resistance may be expected to increase in incidence. Clinicians and microbiologists need to be aware of this emerging problem.
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