By Alexandra Morell, MD
Synopsis: This open-label, randomized controlled trial involving 164 monogamous heterosexual couples demonstrated that for women diagnosed with bacterial vaginosis (BV), concurrent male partner treatment with a combination of oral metronidazole and topical clindamycin resulted in an 43% absolute risk reduction in BV recurrence at 12 weeks, representing a hazard ratio of 0.37 (95% confidence interval, 0.22 to 0.61).
Source: Vodstrcil LA, Plummer EL, Fairley CK, et al. Male-partner treatment to prevent recurrence of bacterial vaginosis. N Engl J Med. 2025;392(10):947-957.
Bacterial vaginosis (BV) is a common vaginal dysbiosis among reproductive-aged women, characterized by a decline in Lactobacillus species and an overgrowth of anaerobic microbes.1 Gardnerella vaginalis, often found in polymicrobial biofilms, commonly is identified in BV cases. BV typically is diagnosed using the Amsel criteria or Nugent scoring.2 Amsel criteria include homogenous, thin, white-gray discharge, greater than 20% clue cells present on microscopy, vaginal fluid pH higher than 4.5, and a positive potassium hydroxide (KOH) whiff test. Three of four criteria must be present to make a diagnosis of BV. This commonly is what is used in the clinical setting. The reference standard for BV diagnosis is Gram stain with Nugent scoring, which, instead, evaluates bacterial morphotypes of vaginal secretions and assigns a score ranging from 0-10 to indicate whether a specific morphotype is considered normal flora, intermediate flora, or suggestive of BV. BV is associated with adverse gynecologic and obstetric outcomes, including pelvic inflammatory disease and preterm birth.1
This was an open-label, randomized controlled trial conducted across five clinical sites in Australia aimed at investigating concurrent female and male partner treatment for BV. The study enrolled symptomatic premenopausal women older than 18 years of age diagnosed with BV using both Amsel criteria and a Nugent score of 4-10. Participants had to be in a monogamous relationship of at least eight weeks with a male partner. Participants were excluded if they could not consent in English, had a current diagnosis of human immunodeficiency virus, or currently were employed as a sex worker.
Women received standard antimicrobial treatment with oral metronidazole 400 mg twice daily for seven days, clindamycin 2% intravaginal cream for seven nights, or 0.75% metronidazole intravaginal gel for five nights. Male partners needed to enroll within one week of their partner and were given oral metronidazole 400 mg twice daily for seven days and topical 2% clindamycin to apply to the penile skin twice daily for seven days. The control group involved standard care for the woman with no treatment for her partner. Couples were randomly assigned in a 1:1 ratio to the partner-treatment group or control group. Randomization was stratified by clinical site, intrauterine device (IUD) use, and male circumcision status. Participants were followed up with clinic visits and home-based sample collections at multiple time points up to 12 weeks.
The primary outcome was BV recurrence within 12 weeks. The study aimed to enroll 342 couples to achieve 80% power to detect a 40% reduction in BV recurrence in the intervention group, assuming a 40% recurrence rate in controls and accounting for a 15% rate of loss to follow-up. A modified intention-to-treat analysis was used, including only participants who received at least one dose of treatment and returned for follow-up. The statistical analysis was performed using Poisson models to estimate recurrence rates per person-year, Kaplan-Meier curves to summarize cumulative recurrence by group, and Cox regression models for hazard ratios. The study also incorporated sensitivity analyses and accounted for the effect of missing data and the COVID-19 pandemic on participant follow-up.
A total of 164 couples were randomized, with 81 assigned to the partner-treatment group and 83 assigned to the control group. Of these, 69 couples in the partner-treatment group and 68 couples in the control group were included in the modified intention-to-treat analysis. The partner-treatment and control groups were similar with respect to age, ethnic background, median number of previous diagnoses of BV, and median number of lifetime male sexual partners. Use of IUDs (28% in partner-treatment vs. 33% in control) and circumcision rate (80% in partner-treatment and control) were comparable between groups.
BV recurrence occurred in 35% of the women in the partner-treatment group (n = 24) vs. 63% in the control group (n = 43). This corresponded to a significantly lower recurrence rate in the partner-treatment group (1.6 vs. 4.2 recurrences per person-year) and a hazard ratio of 0.37 (95% confidence interval [CI], 0.22 to 0.61). In addition, the mean time to recurrence was 19.3 days longer in the partner-treatment group (95% CI, 11.5 to 27.1; P < 0.001). Stratifying by IUD use or circumcision status did not alter the treatment effects.
Among women, the most common adverse events were nausea, headache, and vaginal itch. Adverse events did not differ significantly between the two groups. Forty-six percent of men in the partner-treatment group reported adverse events, with the most common being headache, nausea, and a metallic taste.
Commentary
This randomized trial by Vodstrcil et al represents a promising step forward in the clinical management of BV. Currently, the American College of Obstetricians and Gynecologists (ACOG) recommends treatment with oral metronidazole or intravaginal metronidazole or clindamycin for symptomatic women with BV.2 For patients with contraindications, other treatment options include oral secnidazole, tinidazole, or clindamycin.
Recurrent BV is common and diagnosed in about one-third of patients within three months and approximately 60% within 12 months. Patients with three documented episodes over the course of a year can receive extended suppressive treatment with twice weekly metronidazole gel for 16 weeks following treatment of an acute episode. Historically, treatment of male partners has not been recommended because of lackluster results from earlier studies that relied on single-dose oral therapy and often overlooked adherence and anatomical considerations.3 In contrast to prior studies, this trial used a combined regimen of oral metronidazole and topical clindamycin for male partners and showed a 43% absolute reduction in BV recurrence at 12 weeks.
These findings revitalize the discussion around expedited partner therapy (EPT) for BV. This is a model that has been successful in managing other sexually transmitted infections (STIs). ACOG posits that it is preferable for partners to have a complete clinical evaluation by a provider, but recommends EPT for chlamydia and gonorrhea infections as a method for preventing reinfection when partners are unable or unwilling to undergo clinical assessment.4
Although BV is not formally classified as an STI, the results from this clinical trial underscore its sexual transmission dynamics and the role of the male genital microbiome in recurrence. If feasible, implementing an EPT approach for BV may reduce barriers to partner treatment, especially given that BV is a female-associated dysbiosis of the vaginal microbiome and the diagnostic criteria are specific to women. Additional studies are needed to examine feasibility, patient acceptance, and implementation logistics; however, this study provides support to reconsider partner management strategies in BV.
Alexandra Morell, MD, is Adjunct Instructor, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY.
References
1. Chen X, Lu Y, Chen T, Li R. The female vaginal microbiome in health and bacterial vaginosis. Front Cell Infect Microbiol. 2021;11:631972.
2. [No authors listed]. Vaginitis in nonpregnant patients: ACOG Practice Bulletin, Number 215. Obstet Gynecol. 2020;135(1):e1-e17.
3. Mehta SD. Systematic review of randomized trials of treatment of male sexual partners for improved bacterial vaginosis outcomes in women. Sex Transm Dis. 2012;39(10):822-830.
4. [No authors listed]. ACOG Committee Opinion No. 737: Expedited partner therapy. Obstet Gynecol. 2018;131(6):e190-e193.
This open-label, randomized controlled trial involving 164 monogamous heterosexual couples demonstrated that for women diagnosed with bacterial vaginosis (BV), concurrent male partner treatment with a combination of oral metronidazole and topical clindamycin resulted in an 43% absolute risk reduction in BV recurrence at 12 weeks, representing a hazard ratio of 0.37 (95% confidence interval, 0.22 to 0.61).
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