Comparative Efficacy of Topical Voriconazole With Amphotericin B and Fluconazole in the Treatment of Candida Albicans Keratitis in an Animal Model

Abstract

Abstract: : Purpose: To determine the efficacy of topical Voriconazole with Amphotericin B and Fluconazole in the treatment of experimental Candida Albicans keratitis in an animal model. Methods: The concentrations of the antifungal agents used in this study were based on published recommended levels recommended for parenteral use. Fungal keratitis models were created by injecting into the central cornea of the right eye a 100 ul suspension of Candida Albicans containing 1 X 10 ^6 organisms (colony forming units). Forty four rabbits were randomly divided into four groups and each group was treated hourly for 24 hours with topical voriconazole (10mg/mL), amphotericin B (3mg/mL), fluconazole (2mg/mL), and balanced salt solution (control). Prior to the administration of the last dose, the presence of conjunctival hyperemia and discharge was noted. One hour after administrating the last dose, the animals were sacrificed and a uniform corneal button excised with an 8.5 mm sterile trephine. The corneal buttons were then homogenized, serially diluted and plated on trypticase soy agar. Fungal colony counts were performed after 72 hours incubation at 37 degrees C. Results: Using one–way nonparametric analysis of variance(ANOVA) statistical analysis, fungal colony counts for the initial homogenized samples revealed that only the voriconazole group had a statistically significant reduction in CFU compared to the control group (P 0.02). Comparison of serially dilution 1x10–1 through 1x10–3 demonstrated that the voriconazole, amphotericin B and fluconazole groups all yielded a statistically significant reduction in candid albicans CFU when compared to the control group. Although the average CFU counts were lower for voriconazole than for amphotericin B and fluconazole for each level of dilution, the differences were not statistically significant. The amphotericin B group demonstrated a significant increase in conjunctival hyperemia and mucus discharge compared to the other three groups.Conclusions: Topical voriconazole was found to be as efficacious in the treatment of candida albicans keratitis as the gold standard, amphotericin B with potentially less ocular toxicity. Results suggest that voriconazole is a potential treatment agent against candida albicans keratitis.

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