An assessment of the in vitro antimicrobial effects of two antiepileptic drugs--sodium valproate and phenytoin.

An incidental observation led to the evaluation of the antimicrobial properties of valproate and phenytoin. In vitro inhibition of Mycobacterium smegmatis, Candida albicans, and other standard test organisms by these two antiepileptic drugs was assessed using the broth microdilution procedure. Fluorescence microscopy (Viability Stains, Molecular Probes Inc.) and cultural techniques were employed to distinguish between microbicidal and microbistatic effects. Phenytoin showed no inhibitory activity against the microbes tested. Sodium valproate, on the other hand, was selectively potent against the yeast strains in a dose-dependent manner (MIC = 10-20 microg ml(-1)). In vitro activity against Mycobacterium smegmatis (70% growth inhibition by 81 microg ml(-1)) was moderate to low while Staphylococcus aureus. Pseudomonas aeruginosa and Escherichia coli were not significantly affected. Viability data from fluorescent microscopy and plate cultures correlated well with absorbance (A620nm) growth index, and showed that valproate was microbicidal against susceptible organisms. The mode of action may include blockage of calcium channels and perturbation of membrane potential. This report opens up yet another opportunity for further enquiry into the fundamental mechanisms of drug action and microbial resistance.