In vitro activity of fluconazole, a novel bistriazole antifungal agent

Fluconazole is a novel triazole antifungal agent with excellent activities against a broad range of medically important fungi. The in vitro antifungal activities of fluconazole especially against Candida albicans were examined and the results summarized as follows: 1. Fluconazole was proved to exhibit the highest antifungal activity in synthetic amino-acid medium, fungal (SAAMF), well buffered in a physiologically neutral range. 2. In a exposed time-killing test performed using SAAMF (pH 7.4), the growth inhibition by fluconazole was enhanced in proportion to an increase of fluconazole concentration and 99% inhibition was observed at a concentration of 1 microgram/ml though further increases of concentration up to 80 micrograms/ml failed to demonstrate complete inhibition. 3. Activities of fluconazole against medically important various yeasts were determined by a broth dilution method in SAAMF using the viable counts technique. Among 9 species tested, C. albicans and Candida kefyr were the most sensitive to fluconazole with a IC99 range from 0.20 microgram/ml to 0.39 microgram/ml. On the contrary, Candida glabrata, Cryptococcus neoformans and Trichosporon cutaneum were the least sensitive with a IC99 range from 3.13 micrograms/ml to 12.5 micrograms/ml. 4. Growth inhibition activities of fluconazole against 4 species of Aspergillus were measured on the basis of mycelial protein content. IC50 and IC90 of fluconazole against Aspergillus fumigatus were distributed in the range of 23.9-43.5 micrograms/ml and 50- greater than 100 micrograms/ml, respectively. 5. The anti-Candida activity of fluconazole was little affected by serum concentrations. Fluconazole at a concentration of 0.20 microgram/ml inhibited significantly the mycelial-phase growth and germ tube elongation of C. albicans in a medium supplemented with serum. 6. The germ tube formation and elongation of C. albicans cells engulfed by murine peritoneal exudative cells were significantly affected in a medium containing 1 microgram fluconazole per ml.