Interactions of amphotericin B and SCH 39304 in the treatment of experimental murine candidiasis: lack of antagonism of a polyene-azole combination. Antimicrob. Agents Chemother

Mice infected intravenously with Candida albicans were treated with SCH 39304, a new triazole antifungal compound, amphotericin B, or both. Two dose levels of each drug were evaluated in an attempt to identify potential helpful or harmful effects on survival and kidney colony counts. Contrary to theoretical predictions, combination therapy was not antagonistic and some additive or synergistic effects were observed. The results obtained in this study suggest that antagonism between polyene and azole antifungal drugs is not inevitable and that additive or synergistic effects may be possible. SCH 39304 is a new triazole derivative, with a long half-life and good absorption following oral administration (3). It has been noted to be active in experimental animal models against different fungal pathogens, including As-pergillus species, Candida species, Cryptococcus neofor-mans, Blastomyces dermatitidis, Coccidioides immitis, and other fungi (1, 2, 5, 6, 8). Its major mode of action is thought to be similar to those of other azole antifungal agents, i.e., inhibition of ergosterol synthesis secondary to blocking o