Combination of Miconazole and Domiphen Bromide Is Fungicidal against Biofilms of Resistant Candida spp
Autor: | Paul Cos, Katrijn De Brucker, Kaat De Cremer, Judith Berman, Bruno P. A. Cammue, Karin Thevissen, Jana Tits, Freya Cools, Bert Gevaert, Kristof Verbruggen |
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Rok vydání: | 2020 |
Předmět: |
Pharmacology
Domiphen bromide 0303 health sciences Combination therapy 030306 microbiology Pharmacology. Therapy Biofilm Potentiator Corpus albicans Microbiology Fungicide 03 medical and health sciences Infectious Diseases In vivo medicine Pharmacology (medical) Human medicine Miconazole Biology 030304 developmental biology medicine.drug |
Zdroj: | Antimicrobial agents and chemotherapy |
ISSN: | 1098-6596 0066-4804 |
Popis: | 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. |
Databáze: | OpenAIRE |
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