Combination of Miconazole and Domiphen Bromide Is Fungicidal against Biofilms of Resistant Candida spp.

Autor:	Tits J; Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium., Cools F; Laboratory for Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium., De Cremer K; Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium., De Brucker K; Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium., Berman J; Department of Molecular Microbiology and Biotechnology, School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel., Verbruggen K; Purna Pharmaceuticals, Puurs, Belgium., Gevaert B; Purna Pharmaceuticals, Puurs, Belgium., Cos P; Laboratory for Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium., Cammue BPA; Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium., Thevissen K; Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium karin.thevissen@kuleuven.be.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2020 Sep 21; Vol. 64 (10). Date of Electronic Publication: 2020 Sep 21 (Print Publication: 2020).
DOI:	10.1128/AAC.01296-20
Abstrakt:	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.)
Databáze:	MEDLINE
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