In vitro activity of combinations of antibiotics against Staphylococcus aureus resistant to gentamicin and methicillin.

Twenty clinical isolates of Staphylococcus aureus, resistant to both gentamicin and methicillin, were tested in vitro for sensitivity to rifampicin, novobiocin, fusidic acid, vancomycin, teicoplanin and an extended range of aminoglycosides. Rifampicin was the most active compound tested, having an MIC of less than 0.02 mg/l. All the strains were inhibited by 1 mg/l of novobiocin, vancomycin and teicoplanin, and only one strain was resistant to fusidic acid. 50% of the strains were inhibited by less than 1 mg/l of amikacin and netilmicin, but other aminoglycosides were of poor activity. Resistant mutants were selected when strains were grown in the presence of rifampicin, novobiocin or fusidic acid alone, but this did not occur when rifampicin was combined with either novobiocin or vancomycin. Pharmacokinetic and other considerations suggest that a combination of rifampicin and novobiocin deserves further assessment for the treatment of infections caused by this type of organism.