Repurposing of ribavirin as an adjunct therapy against invasive Candida strains: In vitro study.
Antimicrob Agents Chemother. 2019 Jul 15;:
Authors: Yousfi H, Cassagne C, Ranque S, Rolain JM, Bittar F
The use of antifungal agents in clinical settings is limited by the appearance of drug resistance and adverse side effects. There is, therefore, an urgent need to develop new drugs to strengthen the treatment of invasive fungal diseases. The aim of this study is to describe the potential repurposing of ribavirin as an adjunct therapy against Candida spp.Primary screening of Prestwick chemical library against Candida albicans ATCC 90028 and fluconazole-resistant Candida albicans was performed. Subsequently, we evaluated the response of 100 Candida spp strains to ribavirin, an antiviral agent, using the broth microdilution method as recommended by CLSI. We checked the involvement of efflux pump activity in the development of ribavirin-resistance. We studied time-kill curves and performed a checkerboard assay for ribavirin-antifungals combinations study.Twenty-one nonstandard antifungal compounds were identified, including ribavirin. Ribavirin had, in vitro, an antifungal activity against 63 Candida strains including C. albicans, C. parapsilosis and C. tropicalis, with a minimum inhibitory concentrations (MICs) ranging from 0.37 to 3.02 μg/ml, while MICs for C. krusei, C. glabrata, C. lusitaniae and some C. albicans remain high (≥ 24.16 μg/ml). No relation was observed between efflux pump activity and ribavirin-resistance. Ribavirin exhibited a fungistatic activity against multidrug-resistant (MDR) C. albicans and a fungicidal activity against C. parapsilosis strain. In addition, ribavirin acted synergistically with azoles against Candida strains for which ribavirin MICs were < 24.4 μg/ml.This study highlights the potential clinical application of ribavirin, alone or in association with other antifungal agents, as an adjunct anti-Candida drug.
PMID: 31307986 [PubMed - as supplied by publisher]