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

Jana Tits | Zendy; Freya Cools | Zendy; Kaat De Cremer | Zendy; Katrijn De Brucker | Zendy; Judith Berman | Zendy; Kristof Verbruggen | Zendy; Bert Gevaert | Zendy; Paul Cos | Zendy; Bruno P.A. Cammue | Zendy; Karin Thevissen | Zendy

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

Author(s) -

Jana Tits,

Freya Cools,

Kaat De Cremer,

Katrijn 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 , microbiology and biotechnology , fungicide , miconazole nitrate , antimicrobial , vulvovaginal candidiasis , antifungal , potentiator , medicine , biology , 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.

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