Decreased Susceptibilities to Teicoplanin and Vancomycin among Coagulase-Negative Methicillin-Resistant Clinical Isolates of Staphylococci

Of 41 methicillin-resistant coagulase-negative staphylococcal clinical isolates collected during a 5-month period between late 1995 and early 1996, 28 showed tube dilution teicoplanin MICs of 4 to 8 μg/ml which increased to 16 to 32 μg/ml upon prolonged incubation. Cultures of such bacteria were heterogeneous; they contained subpopulations with frequencies of 10(−5) to 10(−4) that could grow on up to 50 μg of teicoplanin per ml. The same cultures were also heterogeneous with respect to susceptibility to vancomycin; while the MICs for the majority of cells were 2 to 4 μg/ml, subpopulations that could grow on 6 to 12 μg of vancomycin per ml were also present at frequencies of 10(−5) to 10(−7). Selective enrichment of such cultures for the resistant subpopulation occurred with relative ease under laboratory conditions. Heterogeneous phenotypes for teicoplanin (but not for vancomycin) susceptibility were also identified in several Staphylococcus epidermidis isolates collected during the preantibiotic era. The addition of half the MIC of teicoplanin inhibited autolysis and caused formation of cellular aggregates which disintegrated to individual bacteria in the stationary phase when the titer of teicoplanin in the medium fell to undetectable levels, indicating removal of the antibiotic from the culture medium by the bacteria.