Update and Invitro Investigation of Voriconazole Susceptibility for Keratitis and Endophthalmitis Fungal Pathogens

Abstract

Abstract: : Purpose: To update the spectrum and investigate the invitro efficacy of voriconazole vs traditional antifungals against common fungal isolates recovered from cornea and intraocular fluids. Methods: Microbiology database was scanned and fungal isolates associated with keratitis (N=421) and endophthalmitis (122) were extracted and analyzed for classification and isolate frequency. The Sensititre YEASTONE microdilution antifungal susceptibility test (TREK Diagnostics) was used to evaluate susceptibility (MICs) of common fungal pathogens (N=34-20 Candida species, 9 Fusarium species, 4 Aspergillus, and 1 Paecilomyces species ) against amphotericin B, fluconazole, ketoconazole, 5-FC, itraconazole and voriconazole.A standardized suspension was prepared for each test isolate and inoculated in accordance with manufacturer’s instructions. Ten of the test isolates were sent to a reference lab to validate the Sensititre results. Results: The ratio of filamentous fungi (mold) to yeast was 5:1 for keratitis and 1:1 for endophthalmitis. Fusarium species remains the most frequent corneal filamentous pathogen (60.1%) followed by Curvularia species (9.9%), Aspergillus species (8.7%) and Paecilomyces species (5.9%). Colletotrichum species(4.1%) has emerged as the 5^th 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. Aspergillus species (23.3%) were the second most frequent pathogen. Paecilomyces (2.9%) and Philophora (1.9%) were unusual pathogens. Invitro susceptibility profiles were: voriconazole (100%), ketoconazole (82.4%). Amphotericin (76.5%), itraconazole (67%), and 60% for fluconazole and 5-FC. Voriconazole MIC₉₀ were lowest for Candida species (0.016 ug/ml) and highest for Fusarium species (2 ug/ml). Reference lab MICs correlated 100% for yeast isolates (0.016 ug/ml) but were 4 fold higher for Fusarium species (8 ug/ml). MIC₉₀ for Aspergillus species was 0.5 ug/ml. Conclusions: Candida, Fusarium and Aspergillus species remain frequent ocular 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.

Keywords: keratitis • antibiotics/antifungals/antiparasitics • fungal disease