Result per participant.

BackgroundRecurrent vulvovaginal candidiasis (RVVC) is a common condition characterized by frequent relapses, often without a clearly identifiable cause. Fluconazole (FLZ) is the standard treatment but concerns about emerging resistance and drug interaction highlight the need for alternative therapies. Chlorhexidine gluconate (CHG), known for its antifungal and biofilm-disrupting properties, has been proposed as a potential alternative.ObjectiveTo evaluate the efficacy, tolerability, and microbiome impact of a vaginal CHG formulation compared to oral FLZ in the treatment of RVVC caused by Candida albicans.MethodsAn open label randomized non-inferiority trial was conducted to compare vaginal CHG and FLZ treatments. Primary outcome was negative cultures for C. albicans. Resistance profiles and changes in the vaginal microbiome composition were also assessed.ResultsThe study was terminated early due to local irritation associated with CHG and the study design was transitioned into a pilot study. CHG treatment showed comparable efficacy to FLZ in clearing C. albicans infections and preventing recurrences, although the sample size was limited. All 11 participants in the FLZ group cleared the infection after one week treatment, compared to 9 out 11 in the CHG group. No harmful changes to the vaginal microbiome were observed in the CGH or FLZ group. FLZ promoted a shift toward Lactobacillus crispatus dominance, unlike CHG. Notably, 16% of C. albicans isolates exhibited reduced susceptibility or resistance to FLZ.ConclusionDue to the limited number of participants, we cannot conclusively determine whether CHG is non-inferior to FLZ in terms of efficacy for clearing acute C. albicans infections or preventing recurrences. While the current CHG formulation caused local irritation and is not suitable for clinical use, its antifungal and biofilm-inhibiting properties remain promising. Further development of less irritative CHG formulations may offer a valuable alternative for RVVC treatment, particularly in the context of rising FLZ resistance.背景：复发性外阴阴道假丝酵母菌病（Recurrent vulvovaginal candidiasis, RVVC）是一类以频繁复发为特征的常见病症，其病因往往难以明确界定。氟康唑（Fluconazole, FLZ）为该病的标准治疗药物，但随着耐药菌株出现及药物相互作用相关顾虑的凸显，研发替代疗法的需求愈发迫切。葡萄糖酸氯己定（Chlorhexidine gluconate, CHG）因兼具抗真菌活性与生物膜破坏能力，被提出作为潜在的替代治疗方案。 目的：本研究旨在评估阴道用葡萄糖酸氯己定制剂相较于口服氟康唑，在治疗白假丝酵母菌（Candida albicans）所致复发性外阴阴道假丝酵母菌病时的疗效、耐受性及对阴道微生物组的影响。 方法：本研究采用开放标签、随机非劣效性试验设计，对比阴道用CHG与口服FLZ的治疗效果。主要结局指标为白假丝酵母菌培养结果转阴。同时对耐药谱及阴道微生物组组成的变化进行了评估。 结果：本研究因CHG相关的局部刺激反应提前终止，并将试验设计调整为先导性研究。尽管样本量有限，但CHG在清除白假丝酵母菌感染及预防复发方面的疗效与FLZ相当。FLZ组11名受试者接受1周治疗后感染均获清除，而CHG组11名受试者中有9名实现感染清除。两组均未观察到阴道微生物组出现有害改变。FLZ可促使阴道菌群向卷曲乳杆菌（Lactobacillus crispatus）主导的状态转变，而CHG未呈现该效应。值得注意的是，16%的白假丝酵母菌分离株对FLZ表现为敏感性降低或耐药。 结论：由于受试者数量有限，本研究无法明确CHG在清除急性白假丝酵母菌感染及预防复发的疗效上是否非劣于FLZ。尽管当前的CHG制剂存在局部刺激性，不适用于临床应用，但其抗真菌与生物膜抑制活性仍具有开发潜力。针对刺激性更低的CHG制剂的进一步开发，或可为RVVC治疗提供极具价值的替代方案，尤其在FLZ耐药性日益严峻的背景下。