In vitro activity of novobiocin and rifampin alone and in combination against oxacillin-resistant Staphylococcus aureus

Rifampin and novobiocin both have excellent activity against oxacillin-resistant Staphylococcus aureus, but their single use may be associated with the development of resistance. To help predict their clinical value in our institution, 60 recent clinical isolates of oxacillin-resistant S. aureus were studied for in vitro susceptibility to the two agents. Ten isolates with increased MICs to both agents or to rifampin alone were also studied by modified checkerboard and kill-curve methods. Indifference was consistently demonstrated by the checkerboard method and generally found in kill-curve studies. Prevention of development of resistance was demonstrated with the antimicrobial combinations for some isolates. Isolates with increased MICs for the two agents fell into two distinctive groups, with prevention of the development of rifampin resistance occurring in one group but not in the other, suggesting that different strains of oxacillin-resistant S. aureus may have different capacities for development of rifampin resistance.