In non-pregnant patients over the age of 18 with symptomatic bacterial vaginosis, does the addition of oral or vaginal probiotics compared to standard antibiotic use alone, decrease time to recurrence?

Summary of the Issues

Bacterial vaginosis (BV) is the most common cause of symptomatic vaginitis in women of reproductive age, effecting approximately 15 to 50% of cases.^1,2 It is caused by alteration of the vaginal flora resulting in a decrease of lactobacilli and a seven-fold increase in concentration of organisms including Gardnerella vaginalis, Mycoplasma hominis and Prevotella spp. that are frequently found in women with normal vaginal flora.¹ Risk factors include new or multiple sexual partners, frequent douching and social stressors.¹ Complications associated with BV infection include higher risk of pelvic inflammatory disease, premature rupture of membranes in pregnant women and strong association with many sexually transmitted diseases, including HIV, Chlamydia trachomatis and Neisseria gonorrhoeae.²

Current mainstay of treatment for BV is oral or vaginal metronidazole or vaginal clindamycin, but the recurrence rate is as high as 40% within 3 months and 50% within 6 months of treatment.³ It has been proposed that addition of probiotics containing lactobacilli species may increase efficacy of treatment. Probiotics are defined as “live microorganisms which when administered in adequate amounts confer a health benefit to the host.”³

Decreased colonization of lactobacilli allows for over growth of anaerobic bacteria for reasons other than competitive inhibition. Lactobacilli are known to reduce vaginal pH by production of lactic acid, stimulate the immune system and produce hydrogen peroxide.³ It has been documented that adherent biofilms of previously mentioned anaerobic bacteria on vaginal mucosa also contribute to antibiotic resistance and a high recurrence rate. Lactobacilli have been shown in in vitro studies to incorporate into biofilms destroying them.² This review will focus on the role of adding probiotics to currently accepted antibiotic regimens.

Summary of the Evidence

A meta-analysis by Huang et al. looked at 12 randomized control trials (RCTs), a total of 1,304 patients, to evaluate the cure rate of BV when using probiotics versus not. Eight trials used probiotics in combination with antibiotics, the other four looked at cure rates using probiotics alone. Trials were limited to English-language and human trials. Inclusion criteria included RCTs, non-pregnant adults, symptomatic BV, no co-infections, using probiotics (vaginal or oral) compared to placebo or no intervention. Exclusion criteria included patients less than 18, pregnant or infected with HIV or other vaginal infection, insufficient or repeated data, and studies that did not report outcomes of interest.²

Studies were selected by two independent investigators. Quality evaluation of trials were performed by the investigators and validated by Jadad five-point scale. A Jadad score less than or equal to 2 is considered to be low quality and a score greater than or equal to 3 is high quality. Eleven of the 12 studies included were considered high quality according to the Jadad score. These studies included 934 of the total 1,304 patients.²

The included studies were published between 1992 and 2012. They were performed in Italy, Austria, Brazil, Sweden, Belgium, Finland, Africa and China. In 10 of the studies, vaginal probiotics were administered; the remaining two used oral administration. Probiotics were administered in combination with antibiotics in 8 of the 12 RCTs. Follow up time in the selected studies ranged from 4 weeks to 6 months.²

When all 12 trials were pooled there was evidence that probiotic supplementation may significantly improve BV cure rate, however, it is important to mention that statistically significant heterogeneity was observed between groups. The meta-analysis also looked at a subgroup within the original 12 studies. This group consisted of 9 RCTs deemed high-quality by the Jadad scored. These studies consisted of women of European population and used short term follow up (<1 month) to reassess symptoms using Amsel’s criteria. Probiotics were administered either in combination with antibiotics or not. In this subgroup, probiotics were “associated with a significant improvement in cure rate of BV”² whether administered vaginally or orally.²

A RCT by Heczko et al. assessed whether addition of oral probiotics in conjunction with standard antibiotic treatment would decrease recurrence rates compared to antibiotic treatment alone. This was a multicenter, randomized, double-blind placebo controlled study performed in 9 outpatient gynecologic clinics in Poland. Women included in the study 18–50 years of age with histories of recurrent BV and current symptoms. There were five visits (I–V) in the trial. At visit I, women were given standard treatment of metronidazole and randomly assigned to treatment or placebo groups.⁴

Women in the treatment group were given an oral probiotic to take twice daily for 10 days, placebo was administered in the same regimen. Visit II was conducted approximately 14 days after cessation of the probiotic or placebo. At this visit, the women were evaluated for symptoms and another vaginal swab was obtained. If participants still complained of symptoms and G. vaginalis was present, oral clindamycin was administered in conjunction with another round of probiotic or placebo twice daily for 10 days.⁴

Women who were asymptomatic at the second visit were given 10 days of probiotic or placebo once daily for 10 days starting around 18–22 days of their menstrual cycle for 3 months. Women who were treated with a second round of antibiotics were asked to return for an extra visit (II bis), if treatment was successful at that time, they proceeded with the 3 months of probiotics. If treatment was not successful, patients were removed from the trial. Visits III–V were conducted approximately 7 days after the end of each menstrual period. If recurrence of BV was diagnosed at any of the visits, participants ended their participation in the study.⁴

241 of the original 578 participants were compliant with the treatment regimen and comprised the intent-to-treat population. There was no significant difference in the treatment and placebo groups and no participant was excluded for adverse reactions. A significantly longer interval for recurrence of clinical symptoms was noted in the treatment group, but no difference in recurrence interval for microscopic assessment was noted.⁴

Conclusion

Evidence supports addition of probiotics to standard antibiotic treatment to reduce symptomatic recurrences of BV. High rates of heterogeneity between current studies prompts the need for further investigation to standardize probiotic dose, species and regimen before recommendations can be made for or against their use. While no studies were done in the US, the wide range of countries included suggests that outcomes could be applied to women of multiple backgrounds. The probiotics in these studies were shown to be relatively safe with minimal side effects. Therefore, it seems reasonable to add probiotics to the treatment regimens of women suffering from recurrent episodes of BV.