Abstract

Rifampin in combination with other antibiotics has been used successfully in the treat-ment of serious infections due to Staphylococcus epidermidis. The authors evaluated the efficacy of rifampin in combination with either cephalothin, nafcillin, gentamicin, or vancomycin to determine in vitro synergistic or antagonistic interactions of the com-binations and to determine the role of the second antibiotic in preventing the emergence of rifampin-resistant mutants. The authors found that among 10 isolates of methicillin-resistant S. epidermidis, synergy was found in checkerboard studies (inoculum, 105 colony-forming units/ml) for only two isolates and only with nafcillin and rifampin; antagonism was present with one combination for each of four different isolates. Time-kill studies showed each antibiotic capable of preventing the emergence of rifampin-resistant mutants for all 10 isolates, but no synergy or antagonism was present. In ex-perimental endocarditis, however, the addition of cephalothin did not prevent the emergence of rifampin-resistant mutants, and rifampin-resistant mutants were as ca-pable of causing endocarditis as were their rifampin-sensitive parents. Thus, rifampin was a bactericidal antibiotic against methicillin-resistant S. epidermidis. The benefit of