Bacterial vaginosis is a condition associated with adverse reproductive outcomes and characterized by a shift from a Lactobacillus-dominant vaginal microbiota to a polymicrobial microbiota, consistently colonized by strains of Gardnerella vaginalis. Metronidazole is the first-line treatment; however, treatment failure and recurrence rates remain high. To understand complex interactions between Gardnerella vaginalis and Lactobacillus involved in efficacy, here we develop an ordinary differential equation model that predicts bacterial growth as a function of metronidazole uptake, sensitivity, and metabolism. The model shows that a critical factor in efficacy is Lactobacillus sequestration of metronidazole, and efficacy decreases when the relative abundance of Lactobacillus is higher pre-treatment. We validate results in Gardnerella and Lactobacillus co-cultures, and in two clinical cohorts, finding women with recurrence have significantly higher pre-treatment levels of Lactobacillus relative to bacterial vaginosis–associated bacteria. Overall results provide mechanistic insight into how personalized differences in microbial communities influence vaginal antibiotic efficacy.

细菌性阴道病是一种与生殖不良结果相关的疾病，其特征是从乳酸杆菌占优势的阴道菌群向多微生物菌群的转变，该菌群始终由阴道加德纳菌菌株定殖。甲硝唑是一线治疗；但是，治疗失败和复发率仍然很高。为了解阴道加德纳菌与乳杆菌之间涉及功效的复杂相互作用，在此我们建立了一个普通的微分方程模型，该模型可预测细菌的生长与甲硝唑的吸收，敏感性和代谢之间的关系。该模型表明，功效的关键因素是乳酸杆菌乳酸菌的相对丰度较高时，甲硝唑的螯合作用和功效会降低。我们验证了加德纳氏菌和乳杆菌共培养的结果，并且在两个临床队列中，发现相对于细菌性阴道病相关细菌，复发女性的乳杆菌治疗前水平明显更高。总体结果为了解微生物群落的个性化差异如何影响阴道抗生素功效提供了机械原理。