Open AccessCombination of Miconazole and Domiphen Bromide Is Fungicidal against Biofilms of Resistant Candida spp
Author(s) -
Jana Tits,
Freya Cools,
Kaat De Cremer,
Klaas De Brucker,
Judith Berman,
Kristof Verbruggen,
Bert Gevaert,
Paul Cos,
Bruno P. A. Cammue,
Karin Thevissen
Publication year - 2020
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01296-20
Subject(s) - miconazole , biofilm , fungicide , microbiology and biotechnology , potentiator , miconazole nitrate , biology , antifungal , medicine , pharmacology , bacteria , genetics , botany
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.