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.

中文翻译：

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咪康唑和多米芬溴化物的结合对耐药念珠菌属生物膜具有杀真菌作用。

粘膜生物膜相关念珠菌感染的发生和复发是严重的临床问题，例如口腔和外阴念珠菌病。例如，念珠菌引起的阴道感染一生中至少一次影响70％至75％的女性。咪康唑（MCZ）是针对这些真菌感染的首选局部治疗方法，但仅具有中等的抗生物膜活性。通过筛选药物用途的库，我们确定了季铵化合物多米芬溴化物（DB）作为针对假丝酵母生物膜的MCZ增强剂。DB显示出协同的抗白色念珠菌MCZ具有生物膜活性，可将生物膜细胞数量减少1000倍。此外，MCZ-DB组合还导致对吡咯抗性白色念珠菌，光滑念珠菌和耳形念珠菌分离物的生物膜细胞的重大杀伤。在体内，与单一化合物治疗相比，MCZ-DB组合在外阴阴道念珠菌病大鼠模型中具有显着改善的活性。来自人工进化实验的数据表明，没有出现针对该组合的耐药性，这突出表明了MCZ-DB组合疗法在治疗念珠菌生物膜相关感染方面的潜力。