In vitro antifungal activity of nikkomycin Z in combination with fluconazole or itraconazole

Nikkomycins are nucleoside-peptide antibiotics produced by Streptomyces spe cies with antifungal activities through the inhibition of chitin synthesis. We investigated the antifungal activities of nikkomycin Z alone and in com bination with fluconazole and itraconazole. Checkerboard synergy studies we re carried out by a macrobroth dilution procedure with RPMI 1640 medium at pH 6.0. At least 10 strains of the following fungi were tested: Candida alb icans, other Candida spp,, Cryptococcus neoformans, Coccidioides immitis, A spergillus spp,, and dematiacious fungi (including Exophiala jeanselmei, Ex ophiala spinifera, Bipolaris spicifera, Wangiella dermatitidis, Ochroconis humicola, Phaeoannellomyces werneckii, and Cladophialophora bantiana), and 2 strains each of Fusarium, Scedosporium, Paecilomyces, Penicillium, and Tr ichoderma spp. A total of 110 isolates were examined. Inocula of fungal ele ments were standardized by hemacytometer counting or spectrophotametrically . MICs and minimum lethal concentrations (MLCs) were determined visually by comparison of growth in drug-treated tubes with growth in drug-free contro l tubes. Additive and synergistic interactions between nikkomycin and eithe r fluconazole or itraconazole were observed against C. albicans. Candida pa rapsilosis, Cryptococcus neoformans, and Coccidioides immitis. Marked syner gism was also observed between nikkomycin and itraconazole against Aspergil lus fumigatus and Aspergillus flavus. No antagonistic interaction between t he drugs was observed with any of the strains tested.