Mutation frequencies for resistance to fusidic acid and rifampicin in Staphylococcus aureus

Frequencies at which mutants resistant to fusidic acid and/or rifampicin ar ose in vitro were determined in Staphylococcus aureus strains including met hicillin-susceptible S. aureus (MSSA), methicillin-resistant S, aureus (MRS A), vancomycin-intermediate resistant S. aureus (VISA) and hetero-VISA. The concentrations of fusidic acid (30 and 15 mg/L) and rifampicin (16 acid 1 mg/L) used for selection were equal to the expected maximum and minimum ser um concentrations after an oral regimen of rifampicin 900 mg od, together w ith fusidic acid 500 mg tds, Resistant mutants arose at a frequency of arou nd 10(-8) for selections with rifampicin, but were undetectable (frequency < 10(-11)) for selections with fusidic acid. Mutants were not recovered (fr equency < 10(-11)) after selections in the presence of both fusidic acid an d rifampicin at 30/16 and 15/1 mg/L, Our results suggest that these antibio tics, when used in combination, could have a wider role in the management o f staphylococcal infections.