Pharmacodynamics of metronidazole determined by a time-kill assay for Trichomonas vaginalis

Abstract

The pharmacodynamic effects of metronidazole on Trichomonas vaginalis have been poorly characterized. The present in vitro study was performed to characterize the relationship between killing of trichomonads and metronidazole exposure (metronidazole concentration and time of exposure). Five laboratory strains and five recent clinical isolates of T. vaginalis were studied. The minimum lethal concentrations (MLCs) of metronidazole for the strains ranged from 0.8 to 25 micrograms/ml under anaerobic conditions. Metronidazole exhibited concentration-dependent killing against T. vaginalis at concentrations ranging from 0.1 to > 10 times the MLC. The endpoint measurement, the kill rate constant, which was derived from the reduction in the logarithm of the colony count divided by exposure time, compared with the kill rate constant for the growth control was not affected by the time of assessment between 2 and 24 h. The kill rate constant-versus-metronidazole exposure curves were similar when concentration was expressed as a multiple of the MLC. There were no apparent differences between the clinical isolates and laboratory strains. These data suggest that peak metronidazole concentration and/or area under the plasma concentration-versus-time curve are the important pharmacodynamic parameters to be optimized.