Natamycin and voriconazole exhibit synergistic interactions with nonantifungal ophthalmic agents against Fusarium species ocular isolates

Abstract

The in vitro activities of two antifungal drugs in combination with four nonantifungal ophthalmic agents were evaluated using a broth microdilution method and a collection of eight Fusarium ocular isolates that exhibited resistance to both natamycin (MICs, 14 to 32 g/ml) and voriconazole (MICs, 4 to 128 g/ml). Synergistic and indifferent interactions were observed for natamycin and 5-fluorouracil and natamycin with timolol dependent on the Fusarium isolate tested. Isolate-dependent synergistic and indifferent interactions were also observed for natamycin with EDTA and natamycin with dorzolamide. Synergistic or indifferent interactions were observed for voriconazole with timolol and voriconazole with 5-fluorouracil depending on Fusarium isolate. Taken together, these data suggest that commonly used ophthalmic agents enhance the in vitro activity of antifungal drugs against drug-recalcitrant ocular fungal pathogens.