To the content
1 . 2021

Treating male partners of women with bacterial vaginosis (StepUp): a protocol for a randomised controlled trial to assess the clinical effectiveness of male partner treatment for reducing the risk of BV recurrence


Background. Bacterial vaginosis (BV) is estimated to affect 1 in 3 women globally and is associated with obstetric and gynaecological sequelae. Current recommended therapies have good short-term efficacy but 1 in 2 women experience BV recurrence within 6 months of treatment. Evidence of male carriage of BV-organisms suggests that male partners may be reinfecting women with BV-associated bacteria (BV-organisms) and impacting on the efficacy of treatment approaches solely directed to women. This trial aims to determine the effect of concurrent male partner treatment for preventing BV recurrence compared to current standard of care.

Methods. StepUp is an open-label, multicentre, parallel group randomised controlled trial for women diagnosed with BV and their male partner. Women with clinical-BV defined using current gold standard diagnosis methods (≥3 Amsel criteria and Nugent score (NS) = 4-10) and with a regular male partner will be assessed for eligibility, and couples will then be consented. All women will be prescribed oral metronidazole 400 mg twice daily (BID) for 7 days, or if contraindicated, a 7-day regimen of topical vaginal 2% clindamycin. Couples will be randomised 1:1 to either current standard of care (female treatment only), or female treatment and concurrent male partner treatment [7 days of combined antibiotics - oral metronidazole tablets 400 mg BID and 2% clindamycin cream applied topically to the glans penis and upper shaft (under the foreskin if uncircumcised) BID]. Couples will be followed for up to 12 weeks to assess BV status in women, and assess the adherence, tolerability and acceptability of male partner treatment. The primary outcome is BV recurrence defined as ≥3 AmseL criteria and NS = 4-10 within 12 weeks of enrolment. The estimated sample size is 342 couples, to detect a 40% reduction in BV recurrence rates from 40% in the control group to 24% in the intervention group within 12 weeks.

Discussion. Current treatments directed solely to women result in unacceptably high rates of BV recurrence. If proven to be effective the findings from this trial will directly inform the development of new treatment strategies to impact on BV recurrence.

Trial registration. The trial was prospectively registered on 12 February 2019 on the Australian and New Zealand. Clinical Trial Registry (ACTRN12619000196145, Universal Trial Number: U1111-1228-0106, https://

Keywords:bacterial vaginosis, antibiotic treatment, couple treatment, recurrence, metronidazole, clindamycin, StepUp

Vodstrcil L.A., Plummer E.L., Doyle М., Fairley С.К., McGuiness C., Bateson D., et al. Treating male partners of women with bacterial vaginosis (StepUp): a protocol for a randomised controlled trial to assess the clinical effectiveness of male partner treatment for reducing the risk of BV recurrence. BMC Infect Dis. 2020; 20,834.


1. Peebles K., Velloza J., Balkus J.E., McClelland R.S., Barnabas R.V. High global burden and costs of bacterial vaginosis: a systematic review and meta-analysis. Sex Transm Dis. 2019; 46 (5): 304-11.

2. Koumans E.H., Markowitz L.E., Berman S.M., St Louis M.E. A public health approach to adverse outcomes of pregnancy associated with bacterial vaginosis. Int J Gynaecol Obstet. 1999; 67: S29-33.

3. Brotman R.M., Klebanoff M.A., Nansel T.R., Yu K.F., Andrews W.W., Zhang J., et al. Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and tricho-monal genital infection. J Infect Dis. 2010; 202 (12): 1907-15.

4. Cohen C.R., Lingappa J.R., Baeten J.M., Ngayo M.O., Spiegel C.A., Hong T., et al. Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples. PLoS Med. 2012; 9 (6): e1001251.

5. Masson L., Passmore J.A., Liebenberg L.J., Werner L., Baxter C., Arnold K.B., et al. Genital inflammation and the risk of HIV acquisition in women. Clin Infect Dis. 2015; 61 (2): 260-9.

6. Workowski K.A., Bolan G.A. Sexually transmitted disease treatment guidelines, 2015. MMWR Recomm Rep. 2015; 64 (RR-3): 69-72.

7. Oduyebo O.O., Anorlu R.I., Ogunsola F.T. The effects of antimicrobial therapy on bacterial vaginosis in non-pregnant women. Cochrane Database Syst. Rev. 2009; 3: CD006055.

8. Bradshaw C.S., Morton A.N., Hocking J., Garland S.M., Morris M.B., Moss L.M., et al. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J Infect Dis. 2006; 193: 1478-89.

9. Unemo M., Bradshaw C.S., Hocking J.S., de Vries H.J.C., Francis S.C., Mabey D., et al. Sexually transmitted infections: challenges ahead. Lancet Infect Dis. 2017; 17 (8): e235-79.

10. Potter J. Should sexual partners of women with bacterial vaginosis receive treatment? Br J Gen Pract. 1999; 49 (448): 913-8.

11. Gardner H.L., Dukes C.D. Haemophilus vaginalis vaginitis: a newly defined specific infection previously classified non-specific vaginitis. Am J Obstet Gynecol. 1955; 69 (5): 962-76.

12. Swedberg J., Steiner J.F., Deiss F., Steiner S., Driggers D.A. Comparison of single-dose vs one-week course of metronidazole for symptomatic bacterial vaginosis. JAMA. 1985; 254 (8): 1046-9.

13. Vejtorp M., Bollerup A.C., Vejtorp L., Fanoe E., Nathan E., Reiter A., et al. Bacterial vaginosis: a double-blind randomized trial of the effect of treatment of the sexual partner. Br J Obstet Gynaecol. 1988; 95 (9): 920-6.

14. Mengel M.B., Berg A.O., Weaver C.H., Herman D.J., Herman S.J., Hughes V.L., et al. The effectiveness of single-dose metronidazole therapy for patients and their partners with bacterial vaginosis. J Fam Pract. 1989; 28 (2): 163-71.

15. Moi H., Erkkola R., Jerve F., Nelleman G., Bymose B., Alaksen K., et al. Should male consorts of women with bacterial vaginosis be treated? Genitourin Med. 1989; 65 (4): 263-8.

16. Vutyavanich T., Pongsuthirak P., Vannareumol P., Ruangsri R.A., Luangsook P. A randomized double-blind trial of tinidazole treatment of the sexual partners of females with bacterial vaginosis. Obstet Gynecol. 1993; 82 (4 Pt 1): 550-4.

17. Colli E., Landoni M., Parazzini F. Treatment of male partners and recurrence of bacterial vaginosis: a randomised trial. Genitourin Med. 1997; 73 (4): 267-70.

18. Mehta S.D. Systematic review of randomized trials of treatment of male sexual Partners for Improved Bacterial Vaginosis Outcomes in women. Sex Transm Dis. 2012; 39 (10): 822-30.

19. Amaya-Guio J., Viveros-Carreno D.A., Sierra-Barrios E.M., Martinez-Velasquez M.Y., Grillo-Ardila C.F. Antibiotic treatment for the sexual partners of women with bacterial vaginosis. Cochrane Database Syst Rev. 2016; 10: CD011701.

20. Bradshaw C.S., Vodstrcil L.A., Hocking J.S., Law M., Pirotta M., Garland S.M., et al. Recurrence of bacterial vaginosis is significantly associated with post-treatment sexual activities and hormonal contraceptive use. Clin Infect Dis. 2013; 56 (6): 777-86.

21. Vodstrcil L.A., Plummer M.E., Fairley C.K., Tachedjian G., Law M.G., Hocking J.S., et al. Combined oral contraceptive pill-exposure alone does not reduce the risk of bacterial vaginosis recurrence in a pilot randomised controlled trial. Sci Rep. 2019; 9 (1): 3555.

22. Liu C.M., Hungate B.A., Tobian A.A., Ravel J., Prodger J.L., Serwadda D., et al. Penile microbiota and female partner bacterial vaginosis in Rakai, Uganda. mBio. 2015; 6 (3): e00589.

23. Nelson D.E., Dong Q., Van Der Pol B., Toh E., Fan B., Katz B.P., Mi D., et al. Bacterial communities of the coronal sulcus and distal urethra of adolescent males. PLoS One. 2012; 7 (5): e36298.

24. Mehta S.D., Zhao D., Green S.J., Agingu W., Otieno F., Bhaumik R., et al. The Microbiome composition of a man's penis predicts incident bacterial vaginosis in his female sex partner with high accuracy. Front Cell Infect Microbiol. 2020; 10: 433.

25. Mehta S.D., Agingu W., Nordgren R.K., Green S.J., Bhaumik D.K., Bailey R.C., et al. Characteristics of women and their male sex partners predict bacterial vaginosis among a prospective cohort of Kenyan women with non-optimal vaginal microbiota. Sex Transm Dis. 2020; 47 (2): 840-50.

26. Zozaya M., Ferris M.J., Siren J.D., Lillis R., Myers L., Nsuami M.J., et al. Bacterial communities in penile skin, male urethra, and vaginas of heterosexual couples with and without bacterial vaginosis. Microbiome. 2016; 4 (1): 16.

27. Ratten L., Plummer E., Murray G., Danielewski J., Fairley C., Garland S., et al. Sex is associated with the persistence of non-optimal vaginal microbiota following treatment for bacterial vaginosis: a prospective cohort study. BJOG. 2021; 128 (4): 756-67.

28. Swidsinski A., Loening-Baucke V., Mendling W., Dorffel Y., Schilling J., Halwani Z., et al. Infection through structured polymicrobial Gardnerella biofilms (StPM-GB). Histol Histopathol. 2014; 29 (5): 567-87.

29. Mehta S.D., Green S.J., Maclean I., Hu H., Bailey R.C., Gillevet P.M., et al. Microbial diversity of genital ulcer disease in men enrolled in a randomized trial of male circumcision in Kisumu, Kenya. PLoS One. 2012; 7 (7): e38991.

30. Price L.B., Liu C.M., Johnson K.E., Aziz M., Lau M.K., Bowers J., et al. The effects of circumcision on the penis microbiome. PLoS One. 2010; 5 (1): e8422.

31. Gray R.H., Wawer M.J., Serwadda D., Kigozi G. The role of male circumcision in the prevention of human papillomavirus and HIV infection. J Infect Dis. 2009; 199 (1): 1-3.

32. Liu C.M., Hungate B.A., Tobian A.A., Serwadda D., Ravel J., Lester R., et al. Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria. mBio. 2013; 4 (2): e00076.

33. Gray R.H., Kigozi G., Serwadda D., Makumbi F., Nalugoda F., Watya S., et al. The effects of male circumcision on female partners' genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda. Am J Obstet Gynecol. 2009; 200 (1): 42.e1-7.

34. Edwards D.I. Nitroimidazole drugs-action and resistance mechanisms. I. Mechanisms of action. J Antimicrob Chemother. 1993; 31 (1): 9-20.

35. Sobel R., Sobel J.D. Metronidazole for the treatment of vaginal infections. Expert Opin Pharmacother. 2015; 16 (7): 1109-15.

36. Smieja M. Current indications for the use of clindamycin: a critical review. Can J Infect Dis. 1998; 9 (1): 22-8.

37. Amsel R., Totten P.A., Spiegel C.A., Chen K.C., Eschenbach D., Holmes K.K. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. 1983; 74 (1): 14-22.

38. Nugent R.P., Krohn M.A., Hillier S.L. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol. 1991; 29 (2): 297-301.

39. Sobel J.D., Schmitt C., Meriwether C. Long-term follow-up of patients with bacterial vaginosis treated with oral metronidazole and topical clindamycin. J Infect Dis 1993; 167 (3): 783-4.

40. Achilles S.L., Austin M.N., Meyn L.A., Mhlanga F., Chirenje Z.M., Hillier S.L. Impact of contraceptive initiation on vaginal microbiota. Am J Obstet Gynecol. 2018; 218 (6): 622.e1-10.

41. Peebles K., Kiweewa F.M., Palanee-Phillips T., Chappell C., Singh D., Bunge K.E., et al. Elevated risk of bacterial Vaginosis among users of the copper intrauterine device: a prospective longitudinal cohort study. Clin Infect Dis. 2020; Jun 6: ciaa703.

42. Harris P.A., Taylor R., Thielke R., Payne J., Gonzalez N., Conde J.G. Research electronic data capture (REDCap) - a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009; 42 (2): 377-81.

Sukhikh Gennadii Tikhonovich
Academician of the Russian Academy of Medical Sciences, V.I. Kulakov Obstetrics, Gynecology and Perinatology National Medical Research Center of Ministry of Healthсаre of the Russian Federation, Moscow
Savel'eva Galina Mikhailovna
Academician of the Russian Academy of Sciences, MD, Professor, Head of the Subdepartment of Obstetrics and Gynecology of the Pediatric Department of the N.I. Pirogov Russian National Scientific Research Medical University under the Ministry of Health of Russia
Radzinsky Viktor Evseevich
Corresponding Member of the Russian Academy of Sciences, MD, Professor, Head of the Subdepartment of Obstetrics and Gynecology with a Course of Perinatology of the Medical Department in the Russian People?s Friendship University
Medicine today

21-й Всероссийский научно-практический конгресс "Современные технологии катарактальной, рефракционной и роговичной хирургии" Этой осенью российские и зарубежные офтальмологи специалисты соберутся в Москве на одном из самых значимых и масштабных профессиональных мероприятий в...

3 дня, 45 симпозиумов и рекордная явка в онлайне: как прошел 17-й Международный Междисциплинарный Конгресс по Аллергологии и Иммунологии С 23 по 25 июня в Москве на площадке конгресс-зала Radisson Slavyanskaya проходил 17-й Международный Междисциплинарный Конгресс по...

XIV Региональный научно-образовательный форум "Мать и Дитя" и Пленум Правления Российского общества акушеров-гинекологов 28-30 июня 2021 года состоится в очном формате XIV Региональный научно-образовательный форум "Мать и Дитя" и Пленум Правления Российского общества...

Journals of «GEOTAR-Media»