Oral Probiotic Combination for Bacterial Vaginosis

By Donald Brown, ND, Dr. Brown is Founder and Director, Natural Product Research Consultants, Inc.; Advisory Board, American Botanical Council; President's Advisory Board, Bastyr University, Seattle; Advisor to the Office of Dietary Supplements at the National Institutes of Health. Dr. Brown is a consultant for Nature's Way, Inc.

Source: Anukam K, et al. Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: Randomized, double-blind, placebo controlled trial. Microbes Infect 2006;8:1450-1454.

Abstract: In a randomized, placebo-controlled, double-blind trial, the efficacy of an oral probiotic combination was studied in women being treated for bacterial vaginosis (BV) with metronidazole. One hundred and twenty-five premenopausal women (18-44 years old) initially were entered in the study. Patients were diagnosed with BV by the presence of vaginal irritation, discharge and "fishy" odor, and Nugent criteria and detection of sialidase enzyme. All subjects received oral metronidazole (550 mg bid) from days 1 to 7 and were randomized to receive one capsule of Lactobacillus rhamnosus GR-1 (2.5 x 109) and Lactobacillus reuteri RC-14 (2.5 x 109) or placebo orally bid from days 1 to 30. The probiotic combination was supplied by Chris Hansen, Horsholm, Denmark. The primary outcome was the cure of BV as determined by a normal Nugent score, absence of clue cells, negative sialidase test, and no signs or symptoms (no discharge or fishy odor) of BV at day 30.

One hundred six women returned for the 30-day follow-up visit. In the antibiotic/probiotic group, 88% of women were cured compared to 40% in the antibiotic/placebo group (P < 0.001). Of the remaining antibiotic/probiotic subjects (12%), none had BV, but all had mild irritative symptoms, no discharge or odor, a weakly positive sialidase score, and intermediate Nugent score. This contrasted with the remaining 34 antibiotic/placebo subjects, of which half had BV and the other half had an intermediate status. In short, 100% of the probiotic-treated patients no longer were diagnosed with BV, while 30% of the placebo group was positive. High counts of Lactobacillus sp. (> 105 CFU/mL) were recovered from the vagina of 96% of the probiotic-treated subjects compared to 53% of controls at day 30. No adverse events were reported.

Comments

This fascinating study, completed in Nigeria, demonstrates the effectiveness of an oral probiotic combination for improving the outcome of antibiotic treatment for BV. Other studies with antibiotic protocols for the treatment of BV in Caucasian, African-American, European, Asian, and Mexican women have found failure rates as high as 39%.1,2 It's difficult to explain why the failure rate was 60% in this current trial—especially considering that the dose of metronidazole is a standard treatment for BV. Despite these differences, the rate of cure between the probiotic-treated group and placebo group is dramatic. Also of note is the ability of the oral probiotic combination to effectively colonize in the vagina following oral use.

BV is a condition in which the normal vaginal flora changes from a predominance of hydrogen-peroxide-producing Lactobacillus species to high concentrations of a variety of anaerobic organisms such as Gardnerelal vaginalis and Mycoplasma hominis.3 Although the women in the reviewed study above were symptomatic, it is important to realize that a substantial but highly variable number of women are alleged to be asymptomatic. In a study with 2,888 women presenting for routine health care visits in Birmingham. AL, the two classic symptoms of BV, discharge and odor, were reported by a minority of women with BV and only slightly more prevalent than among women without BV.4 Complications arising from BV include increased risk of sexually transmitted diseases and elevated risk of preterm birth and spontaneous abortion.5 Clinical interest therefore extends to not only those women with asymptomatic BV but also prevention of BV.6

Developed by researchers from the University or Western Ontario, the probiotic combination (previously classified as Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14) used in this study is the first to be shown to colonize in the vagina when taken orally.7,8 The two strains originally were isolated from the human female urogenital tract. A randomized, placebo-controlled trial of 64 healthy women (19-46 years old) studied oral use of the combination for 60 days.9 Sixteen of the 64 subjects (25%) were found to have asymptomatic BV at baseline. Among these women, 59% in the probiotic group improved over the 60-day study compared to 31% in the placebo group (P < 0.01). Among the women without BV at baseline who did not have BV, 24% in the placebo group developed BV by day 35 and 56% by day 60 compared to none of the subjects taking the probiotic combination. In addition to a significant increase in vaginal Lactobacillus sp. in the probiotic-treated group, there was a significant decrease in yeast at day 28 (P = 0.01) and significant reduction in coliforms at days 28, 60, and 90 (30 days post-treatment; P = 0.001). No adverse events were reported.

Conclusion

The development of orally viable strains of probiotics may mark a new breakthrough in both the treatment and prevention of BV. With studies demonstrating vaginal colonization after oral use for up to 60 days, the combination of L. rhamnosus GR-1 and L. reuteri RC-14 (Urex-Cap-5, Chris Hansen, Horsholm, Denmark) appears to improve resolution of BV in women being treated with metronidazole and to also potentially decrease risk of BV. Larger and longer trials with a focus on prevention are needed in a more diverse group of women to firmly establish this interesting probiotic combination as a viable clinical option for the prevention and management of BV.

References

1. Hanson JM, et al. Metronidazole for bacterial vaginosis. A comparison of vaginal gel vs. oral therapy. J Reprod Med 2000;45:889-896.

2. Andreeva PM, Omar HA. Effectiveness of current therapy of bacterial vaginosis. Int J Adolesc Med Health 2002;14:145-148.

3. Hill GB. The microbiology of bacterial vaginosis. Am J Obstet Gynecol 1993;169(2 Pt 2):450-454.

4. Klebanoff MA, et al. Vulvovaginal symptoms in women with bacterial vaginosis. Obstet Gynecol 2004;104:267-272.

5. Leitich H, et al. Bacterial vaginosis as a risk factor for preterm delivery: A meta-analysis. Am J Obstet Gynecol 2003;189:139-147.

6. Reid G, Boking A. The potential for probiotics to prevent bacterial vaginosis and preterm labor. Am J Obstet Gynecol 2003;189:1202-1208.

7. Reid G, et al. Probiotic Lactobacillus dose required to restore and maintain a normal vaginal flora. FEMS Immunol Med Microbiol 2001;32:37-41.

8. Morelli L, et al. Utilization of the intestinal tract as a delivery system for urogenital probiotics. J Clin Gastroenterol 2004;38(6 suppl):S107-S110.

9. Reid G, et al. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: Randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol 2003;35:131-134.