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

The frequency of the emergence of ciprofloxacin-resistant mutants to sub-inhibitory concentrations of ciprofloxacin, rifampicin, and ciprofloxacin plus rifampicin were compared in a subcutaneous abscess model of experimental Staphylococcus aureus infection in mice. The in vitro findings showed that the combination of ciprofloxacin and rifampicin was bacteriostatically additive for all strains tested when the combination was examined by the chequer-board technique and fractional inhibitory concentration indices determined. Animals were infected with ciprofloxacin-sensitive and ciprofloxacin-resistant test strains (6989S and 6989R) and left untreated for nine days, which showed that ciprofloxacin resistance had no effect on the pathogenicity of the organisms. In treated animals, ciprofloxacin plus rifampicin was found to be at least as effective as ciprofloxacin alone. However, in the murine model, the combination therapy produced significantly fewer high level ciprofloxacin-resistant mutants than ciprofloxacin alone (p < 0.0005). We conclude that a combination of ciprofloxacin and rifampicin was at least as efficient as either drug alone, and the additional presence of rifampicin reduced the emergence of high level ciprofloxacin-resistant sub-populations in the case of S. aureus subcutaneous abscesses in mice and so the combination may prove to be more efficient than ciprofloxacin alone.