期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 64, 期 10, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01296-20
关键词
Candida; biofilms; combination treatment; domiphen bromide; drug repurposing; fungicidal; miconazole; resistance development; vulvovaginal candidiasis
资金
- Industrial Research Fund (IOF) mandate of the KU Leuven
- VLAIO [HBC.2018.0420, 88555]
- Israel Ministry of Science and Technology
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.
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