重新利用抗疟药：乙胺嘧啶在体外对加德纳菌的活性优于甲硝唑，同时对乳酸杆菌无损害。
Repurposing antimalarials: pyrimethamine exhibits superior in vitro activity to metronidazole against Gardnerella while sparing Lactobacillus.
作者信息
Rosca Aliona S, Chaponda Enesia Banda, Beckers Thalia, De Koning Harry P, Chico R Matthew, Cools Piet
机构信息
Department of Diagnostic Sciences, Laboratory Bacteriology Research, Ghent University, C. Heymanslaan 10, Ghent 9000, Belgium.
Department of Biological Sciences, University of Zambia, Lusaka, Zambia.
出版信息
J Antimicrob Chemother. 2025 Jul 1;80(7):1972-1979. doi: 10.1093/jac/dkaf157.
BACKGROUND
Bacterial vaginosis (BV) is associated with significant reproductive health risks and high recurrence rates after standard antibiotic treatment. Sulfadoxine/pyrimethamine, an antimalarial drug, demonstrated unexpected clearance of BV in clinical trials, suggesting potential antimicrobial effects. Drug repurposing, which leverages existing drugs for new therapeutic applications, offers a promising approach to address the challenges of antimicrobial resistance and high recurrence rates in BV.
OBJECTIVE
To determine the in vitro activity of sulfadoxine/pyrimethamine and its components, sulfadoxine and pyrimethamine, on key species associated with BV.
METHODS
Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined for sulfadoxine/pyrimethamine (20:1 ratio), sulfadoxine, pyrimethamine, and standard-of-care antibiotics, metronidazole and clindamycin, against BV-associated species (Gardnerella spp., Fannyhessea vaginae, Prevotella bivia) and Lactobacillus crispatus (vaginal health marker). Gardnerella biofilms were also exposed to sulfadoxine/pyrimethamine, pyrimethamine, or metronidazole, and biofilm biomass and biofilm cells culturability were assessed.
RESULTS
Sulfadoxine had no effect, while pyrimethamine inhibited all Gardnerella strains with MIC values ranging from 0.125 to 4 mg/L, lower than MICs observed for metronidazole (2-128 mg/L). Pyrimethamine also outperformed metronidazole in inhibiting biofilm mass accumulation and reducing biofilm culturable cells in 3/4 Gardnerella strains. Sulfadoxine/pyrimethamine presented lower MICs than metronidazole for 5/8 Gardnerella strains. Sulfadoxine, pyrimethamine, and sulfadoxine/pyrimethamine showed no activity against other BV-associated species or L. crispatus.
CONCLUSIONS
These findings suggest that pyrimethamine (and sulfadoxine/pyrimethamine) could be promising alternative or adjuvant therapies for BV, warranting further clinical trials.
背景
细菌性阴道病（BV）与重大生殖健康风险相关，且在标准抗生素治疗后复发率较高。磺胺多辛/乙胺嘧啶，一种抗疟药物，在临床试验中显示出对BV意外的清除效果，提示其潜在的抗菌作用。药物重新利用，即将现有药物用于新的治疗应用，为应对BV中的抗菌耐药性挑战和高复发率提供了一种有前景的方法。
目的
确定磺胺多辛/乙胺嘧啶及其成分磺胺多辛和乙胺嘧啶对与BV相关的关键菌种的体外活性。
方法
测定了磺胺多辛/乙胺嘧啶（20:1比例）、磺胺多辛、乙胺嘧啶以及标准治疗抗生素甲硝唑和克林霉素对与BV相关的菌种（加德纳菌属、阴道芬尼希菌、二路普雷沃菌）和卷曲乳杆菌（阴道健康标志物）的最低抑菌浓度（MIC）和最低杀菌浓度。加德纳菌生物膜也暴露于磺胺多辛/乙胺嘧啶、乙胺嘧啶或甲硝唑中，并评估生物膜生物量和生物膜细胞可培养性。
结果
磺胺多辛无作用，而乙胺嘧啶抑制了所有加德纳菌菌株，MIC值范围为0.125至4mg/L，低于甲硝唑观察到的MIC值（2至128mg/L）。在抑制3/4的加德纳菌菌株生物膜质量积累和减少生物膜可培养细胞方面，乙胺嘧啶也优于甲硝唑。对于5/8的加德纳菌菌株，磺胺多辛/乙胺嘧啶的MIC低于甲硝唑。磺胺多辛、乙胺嘧啶和磺胺多辛/乙胺嘧啶对其他与BV相关的菌种或卷曲乳杆菌无活性。
结论
这些发现表明，乙胺嘧啶（以及磺胺多辛/乙胺嘧啶）可能是BV有前景的替代或辅助治疗方法，值得进一步进行临床试验。
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