Combination of miconazole and domiphen bromide is fungicidal against biofilms of resistant candida spp.

Jana Tits, Freya Cools, Kaat de Cremer, Katrijn de Brucker, Judith Berman, Kristof Verbruggen, Bert Gevaert, Paul Cos, Bruno P.A. Cammue, Karin Thevissen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere01296
JournalAntimicrobial Agents and Chemotherapy
Volume64
Issue number10
DOIs
StatePublished - Oct 2020

Keywords

  • Biofilms
  • Candida
  • Combination treatment
  • Domiphen bromide
  • Drug repurposing
  • Fungicidal
  • Miconazole
  • Resistance development
  • Vulvovaginal candidiasis

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