INCREASED OXACILLIN ACTIVITY ASSOCIATED WITH GLYCOPEPTIDES IN COAGULASE-NEGATIVE STAPHYLOCOCCI

Vancomycin resistance in methicillin-resistant staphylococci presents a potential therapeutic problem. In order to understand the impact of low-level vancomycin resistance in coagulase-negative staphylococci, s tepwise selection of vancomycin resistance was accomplished by growing Staphylococcus haemolyticus in culture media with increasing concentr ations of vancomycin. A >40-fold increase in susceptibility to beta-la ctam antibiotics was observed. No obvious alterations in the growth cu rve, the presence of the mecA gene, total DNA restriction fragment len gth polymorphism (RFLP), beta-lactamase production, or the crude prote in fraction were detected in the Staphylococcus haemolyticus-derived c lones when compared to the original isolate. The proportion of the oxa cillin-heteroresistant population also remained similar. A comparable phenomenon occurred with the selection of Staphylococcus epidermidis e xhibiting low-level resistance to vancomycin. Additionally, it was obs erved that clinical isolates of coagulase-negative staphylococci grown in the presence of sub-minimum inhibitory concentrations of either va ncomycin or teicoplanin lost their high-level resistance to oxacillin. Checkerboard tests showed that the combination of vancomycin and oxac illin was synergistic for two isolates of Staphylococcus haemolyticus, two of four isolates of Staphylococcus epidermidis, and one isolate o f Staphylococcus hominis.