Efficacy of Rezafungin on Candida albicans Endophthalmitis in a Rabbit Model

TL;DR

Rezafungin effectively treats Candida albicans endophthalmitis in rabbits, reducing fungal burden and eye damage better than other antifungals.

Contribution

Demonstrates rezafungin's superior efficacy against fungal eye infections in a rabbit model compared to existing treatments.

Findings

Rezafungin at 10 mg/kg eliminated fungal growth in eye tissues and reduced kidney fungal burden.

Micafungin and voriconazole failed to clear fungal infections and caused significant eye lesions.

Rezafungin showed no eye lesions, indicating its protective effect against C. albicans-induced damage.

Abstract

Endophthalmitis, a severe infection of the intraocular tissues that can result in permanent loss of vision if not immediately treated, is often caused by fungi, namely Candida albicans. Treatment options are limited due to a lack of ocular penetration of antifungal drugs. Rezafungin, an echinocandin antifungal with a long half-life, which was recently approved by the US Food and Drug Administration (FDA), has shown efficacy against candidiasis.

In this study, using a rabbit model, we compared rezafungin, micafungin, and voriconazole in a hematogenous C. albicans endophthalmitis rabbit model. Fungal burden was determined in the aqueous humor, vitreous humor, choroid-retina, and the kidneys of infected rabbits; eye lesions were visualized by indirect ophthalmoscopy.

No fungal growth was detected in the aqueous humor, vitreous humor, or choroid-retina of rabbits treated with 10 mg/kg rezafungin at the time of fungal inoculation. Additionally, rabbits given 10 mg/kg rezafungin showed the lowest kidney fungal burden (average log colony-forming units [CFUs]/g of < 0.5). In contrast, animals given either micafungin (6.2 mg/kg) or voriconazole (10 mg/kg) in the same treatment regimen were positive for fungal infection as measured by CFUs in each of these areas, demonstrating fungal burden. Additionally, significant increases in eye lesion scores were observed in rabbits given either micafungin or voriconazole, while no eye lesions were noted in rabbits that received rezafungin.

Taken together, these results indicate that rezafungin was effective at reducing the acute fungal burden and subsequent eye lesions caused by C. albicans-induced endophthalmitis.

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