Combination of Miconazole and Domiphen Bromide Is Fungicidal against Biofilms of Resistant Candida spp.
Jana TitsFreya CoolsKaat De CremerKatrijn De BruckerJudith BermanKristof VerbruggenBert GevaertPaul CosBruno P A CammueKarin ThevissenPublished in: Antimicrobial agents and chemotherapy (2020)
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.
Keyphrases
- candida albicans
- biofilm formation
- combination therapy
- induced apoptosis
- cell cycle arrest
- risk assessment
- type diabetes
- endoplasmic reticulum stress
- signaling pathway
- machine learning
- big data
- pseudomonas aeruginosa
- pregnant women
- cell proliferation
- skeletal muscle
- artificial intelligence
- pregnancy outcomes
- deep learning
- climate change
- replacement therapy
- wound healing