INTERACTION OF SUB-INHIBITORY CONCENTRATIONS OF CIPROFLOXACIN AND RIFAMPICIN AGAINST STAPHYLOCOCCUS-AUREUS

The frequency of the emergence of ciprofloxacin-resistant mutants to s ub-inhibitory concentrations of ciprofloxacin, rifampicin, and ciprofl oxacin plus rifampicin were compared in a subcutaneous abscess model o f experimental Staphylococcus aureus infection in mice. The in vitro f indings showed that the combination of ciprofloxacin and rifampicin wa s bacteriostatically additive for all strains tested when the combinat ion was examined by the chequer-board technique and fractional inhibit ory concentration indices determined. Animals were infected with cipro floxacin-sensitive and ciprofloxacin-resistant test strains (6989S and 6989R) and left untreated for nine days, which showed that ciprofloxa cin resistance had no effect on the pathogenicity of the organisms. In treated animals, ciprofloxacin plus rifampicin was found to be at lea st as effective as ciprofloxacin alone. However, in the murine model, the combination therapy produced significantly fewer high level ciprof loxacin-resistant mutants than ciprofloxacin alone (p < 0.0005). We co nclude that a combination of ciprofloxacin and rifampicin was at least as efficient as either drug alone, and the additional presence of rif ampicin reduced the emergence of high level ciprofloxacin-resistant su b-populations in the case of S. aureus subcutaneous abscesses in mice and so the combination may prove to be more efficient than ciprofloxac in alone.