Combination of miconazole and domiphen bromide is fungicidal against biofilms of resistant Candida spp.

The occurrence and recurrence of mucosal biofilm-related Candida infections, such as oral and vulvovaginal candidiasis, is a serious clinical issue. Vaginal infections caused by Candida spp., for example, affect 70-75% of women at least once during their lives. Miconazole (MCZ) is the preferred topical treatment against these fungal infections, yet it has only moderate antibiofilm activity. Through screening of a drug repurposing library we identified the quaternary ammonium compound domiphen bromide (DB) as a MCZ potentiator against Candida biofilms. DB displayed synergistic C. albicans antibiofilm activity with MCZ, reducing viable biofilm cells 1000-fold. In addition, the MCZ-DB combination also resulted in significant killing of biofilm cells of azole-resistant C. albicans, C. glabrata, and C. auris isolates. In vivo, the MCZ-DB combination had significantly improved activity in a vulvovaginal candidiasis rat model as compared to single compound treatments. Data from an artificial evolution experiment indicated that resistance development against the combination was not occurring, highlighting the potential of MCZ-DB combination therapy to treat Candida biofilm-related infections.