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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.

Quantitative modeling predicts mechanistic links between pre-treatment microbiome composition and metronidazole efficacy in bacterial vaginosis