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, stepwise selection of vancomycin resistance was accomplished by growing Staphylococcus haemolyticus in culture media with increasing concentrations of vancomycin. A >40-fold increase in susceptibility to beta-lactam antibiotics was observed. No obvious alterations in the growth curve, the presence of the mecA gene, total DNA restriction fragment length polymorphism (RFLP), beta-lactamase production, or the crude protein fraction were detected in the Staphylococcus haemolyticus-derived clones when compared to the original isolate. The proportion of the oxacillin-heteroresistant population also remained similar. A comparable phenomenon occurred with the selection of Staphylococcus epidermidis exhibiting low-level resistance to vancomycin. Additionally, it was observed that clinical isolates of coagulase-negative staphylococci grown in the presence of sub-minimum inhibitory concentrations of either vancomycin or teicoplanin lost their high-level resistance to oxacillin. Checkerboard tests showed that the combination of vancomycin and oxacillin was synergistic for two isolates of Staphylococcus haemolyticus, two of four isolates of Staphylococcus epidermidis, and one isolate of Staphylococcus hominis.