Efficacy of Rezafungin on Candida albicans Endophthalmitis in a Rabbit Model

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Published: Oct 21, 2025
Keywords:
Rezafungin, Candida albicans, Fungal Endophthalmitis, Echinocandin, Ocular Fungal Infection, Invasive Candidiasis

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John Saghir
Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology Case Western Reserve University, Cleveland, Ohio
Janet Herrada
Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology Case Western Reserve University, Cleveland, Ohio
Lisa Long
Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology Case Western Reserve University, Cleveland, Ohio
Erin San Valentin
Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology Case Western Reserve University, Cleveland, Ohio
Thomas S. McCormick
Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology Case Western Reserve University, Cleveland, Ohio
Mahmoud A. Ghannoum
Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology Case Western Reserve University; University Hospital Cleveland Medical Center, Cleveland, Ohio

Abstract

Background: 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. 


Methods: 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. 


Results: 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. 


Conclusion: 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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Vol. 10 No. 2 (2025): Volume 10, Number 2
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Author Biography

Mahmoud A. Ghannoum, Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology Case Western Reserve University; University Hospital Cleveland Medical Center, Cleveland, Ohio

-American University of Beirut, Beirut, Lebanon, B.Sc. -Loughborough University of Technology, Loughborough, England, M.Sc. -Weatherhead School of Management, Case Western Reserve University, Cleveland, OH, Executive MBA Mahmoud Ghannoum, Ph.D., MBA, FIDSA, joined Case Western Reserve University and University Hospitals Cleveland Medical Center in 1996 from prior positions at the UCLA School of Medicine and Kuwait University. Dr. Ghannoum has spent his entire academic career studying medically important fungi encompassing different fungal pathogens including Candida, Aspergillus and Cryptococcus, the major causes of fungal infections. He published more than 250 peer-reviewed articles addressing various aspects of superficial and systemic fungal infections. Recently he published the first study describing the oral mycobiome of health individuals. He has published extensively in the area of fungal pathogenesis with special focus on virulence factors including phospholipase B, germination, adhesion, and biofilm formation, both in vitro and in vivo. Dr. Ghannoum is a Professor and Director of the Center for Medical Mycology at Case Western Reserve University and University Hospitals Cleveland Medical Center. The center of excellence that Dr. Ghannoum directs is a multidisciplinary center that combines basic and translational research investigating fungi from the test tube to the bedside. He has performed several studies investigating the mechanisms underlying Candida pathogenesis. He is the recipient of the Freedom to Discover Award from Bristol-Myers Squibb, th4e Billy Cooper Award from the Medical Mycological Society of the Americas. In 2009 he was appointed as the Chairman of the Subcommittee on Antifungal Susceptibility Testing, Clinical Laboratory Standards Institute. In 2013, he was appointed as an Advisor to the CLSI Consensus Microbiology Committee, and was selected as “Most Interesting Person” by Cleveland Magazine. Dr. Ghannoum has been involved in preclinical and clinical studies evaluating the efficacy of antifungals. He has in-depth interest and expertise in oral complications of HIV/AIDS, particularly oral candidiasis, and acted as the Chair of the Oral HIV-AIDS Research Alliance (OHARA) and the PI of OHARA’s Medical Mycology Unit based at Case. Recently, Dr. Ghannoum has been involved in characterizing the oral microbiome in health and disease, specifically has pioneered characterization of the human mycobiome (the fungal component of the human microbiota that make up the normal flora in HIV patients). This research may identify relationships between fungal species and their effect on various human diseases. Dr. Ghannoum is a successful entrepreneur, having co-founded multiple companies that have raised millions of dollars and commercialized products.

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