In vitro investigation of voriconazole susceptibility for keratitis and endophthalmitis fungal pathogens

Purpose To update the spectrum of ocular fungal isolates and investigate the in vitro efficacy of voriconazole and other antifungals. Design Experimental study. Methods Microbiology database was scanned and fungal isolates associated with keratitis (419) and endophthalmitis (122) were analyzed for classification and isolate frequency. The Sensititre YeastOne microdilution antifungal susceptibility test was used to evaluate susceptibility (MICs) of 34 common fungal pathogens against amphotericin B, fluconazole, ketoconazole, 5-flucytosine, itraconazole, and voriconazole. Ten of the test isolates were sent to a reference laboratory to validate the Sensititre results. Results Fusarium species remains the most frequent corneal fungal pathogen (60.1%). Colletotrichum species (4.1%) has emerged as the fifth most common mold in keratitis. Top yeast isolates from cornea included Candida albicans (52.3%) and Candida parapsilosis (37.3%). Half of the intraocular pathogens were Candida species. Paecilomyces (2.9%) and Philophora (1.9) were unusual pathogens. In vitro susceptibility profiles were voriconazole (100%), ketoconazole (82.4%), amphotericin (76.5%), itraconazole (67%), fluconazole (60%), and 5-FC (60%). Voriconazole MIC₉₀ were lowest for Candida species (0.016 μg/ml) and highest for Fusarium species (2 μg/ml). Reference laboratory MICs correlated 100% for yeast isolates (0.016 μg/ml) but were fourfold higher for Fusarium species (8 μg/ml). MIC₉₀ for Aspergillus species was 0.5 μg/ml. Conclusions Candida, Fusarium, and Aspergillus species remain frequent fungal pathogens. Voriconazole may have a role in the therapeutic management of Candida and Aspergillus ocular infections. Clinical efficacy must determine the role for other fungal pathogens. Human use and animal models will determine its use in the clinical setting.