Intravitreal Rezafungin and Anidulafungin in a Rabbit Model of Aspergillus fumigatus Endophthalmitis

Rezafungin (RZF) and anidulafungin (AFG) are echinocandins with potential for treating Aspergillus fumigatus endophthalmitis. We evaluated their antifungal and anti-inflammatory effects in vitro and in a rabbit endophthalmitis model. In vitro, minimum effective concentrations and minimum inhibitory concentrations were determined, biofilm inhibition was assessed, and drug-induced structural damage was examined by confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy. TNF-α and IL-1β mRNA levels in RAW 264.7 macrophages were measured to assess inflammatory regulation. In vivo, a rabbit model of A. fumigatus endophthalmitis was established and, 24 hours after infection, eyes received a single intravitreal injection of liposomal amphotericin B, voriconazole, RZF, AFG or normal saline. Clinical inflammation scores, intraocular fungal burden, aqueous humor TNF-α levels and histopathological changes were compared among groups. RZF and AFG showed low minimum effective concentrations, inhibited biofilm formation, disrupted fungal cell wall and membrane integrity in vitro and significantly reduced intraocular inflammation, fungal burden and aqueous humor TNF-α in vivo, with overall efficacy comparable to that of liposomal amphotericin B and voriconazole. These findings support RZF and AFG as promising alternative agents for intravitreal therapy of A. fumigatus endophthalmitis.