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The efficacy of rifampicin against Staphylococcus aureus in vitro and in an experimental infection in normal and granulocytopenic mice.

The effect of rifampicin on Staphylococcus aureus in vitro was assessed as the difference between the logarithms of the numbers of colony forming units (CFU) with and without 3 h of exposure to the drug. The efficacy was expressed as the EC50, i.e. the concentration at which 50% of the maximal effect was obtained, calculated according to the Hill equation. The value found for the EC50 was 3.8 micrograms/l and the mean maximal effect was a log ratio of 5.03 (SEM 0.33). In vivo experiments were performed in normal mice and in mice made granulocytopenic by irradiation. The effect of rifampicin was assessed as the CFU count 5 h after the injection of a suspension of bacteria into the thigh muscle and 4 h after the administration of rifampicin. The efficacy was expressed as the ED50, i.e. the dose at which 50% of the maximal effect is obtained. This value was 0.18 mg/kg for the normal mice and 0.15 mg/kg for the granulocytopenic mice. The corresponding mean plasma concentrations of non-protein-bound drug were 28 and 24 mg/l, respectively. Thus, the EC50 was found to be much higher in vivo than that in vitro. This difference should be taken into account when parameters of in-vitro efficacy are applied to establish dosage schedules.