Efficacy of Antibiotic Combinations Including Rifampin Against Methicillin-Resistant Staphylococcus epidermidis: In Vitro and in Vivo Studies

Abstract

Rifampin in combination with other antibiotics has been used successfully in the treatment 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 combinations and to determine the role of the second antibiotic in preventing the emergence of rifampin-resistant mutants. The authors found that among 10isolates 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. Timekill 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 experimental endocarditis, however, the addition of cephalothin did not prevent the emergence of rifampin-resistant mutants, and rifampin-resistant mutants were as capable of causing endocarditis as were their rifampin-sensitive parents. Thus, rifampin was a bactericidal antibiotic against methicillin-resistant S. epidermidis. The benefit of a second antibiotic in vitro was the prevention of the emergence of rifampin-resistant mutants. However, in vivo results with a f3-lactam antibiotic did not confirm in vitro observations. More animal and human studies should be performed with antibiotic combinations including rifampin against methicillin-resistant S. epidermidis.