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Infectious Diseases in Obstetrics and Gynecology
Volume 2018, Article ID 7040498, 10 pages
https://doi.org/10.1155/2018/7040498
Research Article

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

Cidara Therapeutics, Inc., San Diego, CA, USA

Correspondence should be addressed to Jeffrey B. Locke; moc.aradic@ekcolj

Received 12 July 2017; Accepted 17 January 2018; Published 22 February 2018

Academic Editor: Bryan Larsen

Copyright © 2018 Jeffrey B. Locke et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.