Clindamycin treatment for Bacterial Vaginosis: Identifying Subpopulations with EnhancedTherapeutic Outcomes

About This Grant

PROJECT SUMMARY/ABSTRACT This proposal presents a five-year research career development program focused on the study of the vaginal microbiome and its contributions to bacterial vaginosis (a highly recurrent and common gynecologic condition), with the goal of expanding knowledge on mechanisms for treatment failure and better informing future therapies. The candidate is currently an Assistant Professor of Gynecology and Obstetrics at Johns Hopkins University School of Medicine. The outlined proposal builds on the candidate’s previous clinical experience in recurrent vaginitis and integrates new domains of expertise in clinical investigation, the vaginal microbiome, ‘omics analysis, and bioinformatics. The proposed analyses and didactic work will position the candidate with a unique set of cross disciplinary skills that will enable her to transition to independence as a physician scientist. Bacterial vaginosis (BV), an alteration of the vaginal microbiome associated with vaginal discharge and odor, affects one-third of reproductive age women. BV has been correlated with adverse outcomes including preterm birth and increased risk of STI/HIV acquisition. It is unfortunately highly recurrent, with 25% of individuals experiencing recurrence within 6 weeks of initial treatment and 60% within 1 year. Mechanisms for these poor outcomes are not well understood, though recent data suggests that resistance to metronidazole (the most commonly prescribed antibiotic for treatment) and Lactobacillus iners may play a role. The proposed research aims to evaluate if these mechanisms are responsible for poor treatment outcomes and whether clindamycin, the less commonly prescribed antibiotic for BV, may be more effective than metronidazole for certain individuals. Clindamycin is hypothesized to be superior to metronidazole in those with metronidazole resistance, and for those with Lactobacillus iners present prior to treatment, as it targets lactobacilli while metronidazole does not. Theoretically, eliminating Lactobacillus iners, which is associated with frequent BV recurrences, may allow for a more favorable Lactobacillus spp. to populate (L. crispatus, L. jensenii, L. gasseri: all associated with fewer BV occurrences). The proposed aims will 1) determine the impact of clindamycin treatment on the vaginal microbiota, focusing on Lactobacillus spp. post-treatment, 2) use metagenomics to identify markers of metronidazole resistance and presence of L. iners pre- and immediately post- treatment, relating these factors to clinical outcomes over 6 weeks, and 3) recruit a cohort of individuals with recurrent BV who are treated with clindamycin, following closely with frequent vaginal sampling for 6 weeks post-treatment, characterizing microbiome changes following treatment (specifically timing of Lactobacillus repopulation). The scientific objective is to help inform future BV therapeutic approaches by identifying if clindamycin is a preferred treatment either: 1) for a subset of individuals with BV (those with metronidazole resistance or L. iners present prior to treatment) or 2) as pre-treatment prior to novel therapies such as live biotherapeutics (e.g., vaginal probiotics) which aim to introduce favorable Lactobacillus spp. to the vaginal microbiome.