A comparison of bifonazole (BAY H 4502) with clotrimazole in vitro

The antifungal activity of a new topical imidazole, bifonazole (BAY h 4502, Bayer AG Institute for Chemotherapy), was compared in vitro with that of clotrimazole (BAY b 5097, Schering Corporation) in tests with 67 pathogenic and commensal yeasts, 45 dermatophytes and 14 miscellaneous pathogenic fungi by an agar dilution method. Three media, Kimmig's agar, Sabouraud's agar, and casein-yeast extract-glucose agar were used. Bifonazole was inhibitory for nearly all the yeasts tested including Candida albicans, C. parapsilosis, and Torulopsis glabrata with geometric mean minimal inhibitory concentrations (G-MIC) averaging 5 micrograms ml-1 on all three media. Clotrimazole was the more active drug against these same species with G-MIC's ranging from 0 . 25 to 2 . 10 micrograms ml-1. Results with bifonazole were affected by choice of medium with Kimmig's agar generally giving the lowest MIC's; results with clotrimazole were also affected by choice of medium but to a lesser degree. In nearly all instances, both bifonazole and clotrimazole were inhibitory for the dermatophytic fungi at concentrations of 0 . 50 micrograms ml-1 or less and clotrimazole was the more active drug. Choice of medium was, in general, not a factor with these latter fungi which included Epidermophyton, Trichophyton, and Microsporum species. Both drugs were active against species of Aspergillus (G-MIC's of 3 . 18 micrograms ml-1), Fusarium (G-MIC's ranging from 1 . 59 to 12 . 70 micrograms ml-1) and Scopulariopsis (G-MIC's of 1 . 78 micrograms ml-1); clotrimazole was the more active drug by factors of 2- to 4-fold on all three media. Bifonazole MICs were shown to vary with pH (maximal activity at pH 6 . 5) with selected yeasts when tested on Kimmig's agar. Differences in results obtained with varying inoculum sizes for these same yeasts generally were unremarkable. With selected species of yeasts and dermatophytes, it was determined that the ratio of minimal fungicidal to inhibitory concentrations (MFC/MIC) was much lower for bifonazole than for clotrimazole.