Time-dependent killing of Clostridium difficile by metronidazole and vancomycin

Killing of Clostridium difficile by metronidazole and vancomycin was studied with a batch culture method. Pre-reduced 50 ml volumes of brain heart infusion broth containing one of a range of concentrations of either vancomycin or metronidazole were inoculated with approximately 10(6) cfu/ml of C. difficile. The cultures were incubated anaerobically at 35 degrees C for 24 h. Total viable counts and spore counts were performed with a modified Miles and Misra technique. Concentrations of metronidazole and vancomycin below the respective MICs had no effect on the growth of C. difficile. A significant reduction in numbers of vegetative cells and spores occurred in the presence of concentrations of both agents close to their respective MICs. A bacteriostatic effect was observed when vancomycin concentrations similar to those occurring in faeces following oral administration of the drug were used. In contrast, rapid killing of vegetative cells occurred over a wide range of metronidazole concentrations greater than the MIC.