1. Combination of Miconazole and Domiphen Bromide Is Fungicidal against Biofilms of Resistant Candida spp.
- Author
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Tits J, Cools F, De Cremer K, De Brucker K, Berman J, Verbruggen K, Gevaert B, Cos P, Cammue BPA, and Thevissen K
- Subjects
- Animals, Antifungal Agents pharmacology, Antifungal Agents therapeutic use, Biofilms, Candida albicans, Female, Humans, Microbial Sensitivity Tests, Quaternary Ammonium Compounds, Rats, Candida, Miconazole pharmacology
- Abstract
The occurrence and recurrence of mucosal biofilm-related Candida infections, such as oral and vulvovaginal candidiasis, are serious clinical issues. Vaginal infections caused by Candida spp., for example, affect 70 to 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 an MCZ potentiator against Candida biofilms. DB displayed synergistic anti- Candida albicans biofilm activity with MCZ, reducing the number of viable biofilm cells 1,000-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 compared to that of single-compound treatments. Data from an artificial evolution experiment indicated that the development of resistance against the combination did not occur, highlighting the potential of MCZ-DB combination therapy to treat Candida biofilm-related infections., (Copyright © 2020 American Society for Microbiology.)
- Published
- 2020
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