Time-Kill Kinetics of Rezafungin (CD101) in Vagina-Simulative Medium for Fluconazole-Susceptible and Fluconazole-Resistant Candida albicans and Non-albicans Candida Species

Abstract

Background. While echinocandins demonstrate excellent efficacy against Candida species in disseminated infections and demonstrate potent minimal inhibitory concentration (MIC) values under standard susceptibility testing conditions, investigation under conditions relevant to the vaginal environment was needed. We assessed the antifungal activity and time-kill kinetics of the novel echinocandin rezafungin (formerly CD101) under such conditions, against Candida species relevant to vulvovaginal candidiasis (VVC). Methods. Susceptibility testing of fluconazole-susceptible and fluconazole-resistant C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei was performed in RPMI at pH 7.0 and in vagina-simulative medium (VSM) at pH 4.2 for topical rezafungin, terconazole, fluconazole, and amphotericin B. Time-kill kinetics were evaluated for rezafungin and terconazole at 2, 8, 32, and 128 μg/ml over 72 hours. Results. Rezafungin MIC values were the same or 2-fold higher in VSM/pH 4.2 versus RPMI/pH 7.0. Some C. albicans terconazole MIC values were lower, but most were significantly higher in VSM than in RPMI. Rezafungin was fungicidal against 11/14 strains and near-fungicidal against the others. Terconazole (128 μg/ml) was fungicidal against C. krusei and near-fungicidal against susceptible C. parapsilosis but fungistatic versus all other strains evaluated. Conclusion. Rezafungin retained anti-Candida activity and fungicidal activity under in vitro conditions relevant to VVC.