Bacterial Vaginosis (Part 3 of 3)

Alternative and Emerging Treatments

Angela Kelly, MA and Michael Stanclift, ND
This is the last installment of a three-part series on bacterial vaginosis (BV). In part one, we discussed a healthy vaginal microbiome, symptoms, and diagnostic criteria. In part two , we highlighted the risk factors that contribute to BV, the health impacts it can cause, and conventional antimicrobial treatments, along with their propensity for resistance.

As we saw in part two , conventional antimicrobials often only temporarily resolve BV, and contribute to antibiotic resistance. For this reason, many patients turn to alternative treatments. In addition, new therapeutics are appearing and some show great promise. It is important to note that treatments such as boric acid, prebiotics, garlic, vaginal microbiome transplantation, Zataria Multiflora cream, vitamin C, antiseptics, and seaweed extracts have limited clinical data to support their use.  However, multiple clinical trials can be found supporting the use of probiotics for the treatment of BV.

Boric acid
Though toxic if taken orally, boric acid administered intravaginally has been used to treat vaginal infections for over 100 years.1 It can lower the rate of BV recurrences when used as a complementary therapy to antimicrobials.2 A recent study shows the potential for boric acid as a standalone treatment for BV.3 Side effects are uncommon (< 10% of cases) but include watery discharge during treatment, vaginal burning sensations, and vaginal erythema.4

Prebiotics
Prebiotics feed beneficial microorganisms. In a randomized double-blind study from 2012, a prebiotic gel containing prebiotics from the glucooligosaccharides (GOS) family was shown to quickly restore the vaginal microbiota.5 Additionally a clinical study from 2017 showed that prebiotic gels may also improve the success of BV treatments.6

Garlic
A 2013 study comparing garlic tablets to oral metronidazole found that garlic tablets were as effective as metronidazole with far fewer reported side effects.7 Side effects of garlic tablets were more tolerable than metronidazole and included heartburn and nausea.7

Vaginal microbiome transplantation
Vaginal microbiome transplantation (VMT) involves seeding a recipient’s vaginal microbiome with the bacteria from a healthy donor. A 2019 study of VMT successfully treated four out of five participants with intractable and recurrent BV.8 In some cases, multiple VMT treatments may be necessary.8

Zataria multiflora cream
Also known as Shirazian thyme, Zataria multiflora is a plant native to Iran, Afghanistan, and Pakistan. The plant’s essential oil contains thymol and carvacrol, which have antibacterial properties.9 A 2008 clinical trial revealed Zataria multiflora vaginal cream to be as effective in treating BV as metronidazole vaginal cream.9 Adverse side effects of treatment included nausea, vaginal dryness, and burning.

Vitamin C
In a 2011 clinical trial it was shown that when administered intravaginally, silicon-coated vitamin C tablets were as effective as metronidazole gel in treating BV and were beneficial in preventing recurrences.10 However, not all participants were able to tolerate treatment due to itching, burning, and pain.10

Antiseptics
In a study of patients with recurrent BV, Octenidine showed high initial cure rates over 87%; however, the development of bacterial resistance to Octenidine was very high with 37.5% of patients showing complete resistance at three treatments/one-year follow-ups.11 At six months the relapse rate of patients included in this study were as high as 66.6%.11

Seaweed extracts
Preclinical research found that ethanol extract of green seaweed (U. Pertusa) possesses robust antimicrobial activity against G. vaginalis, which may have potential as a future treatment for BV.12

Probiotics: Lactobacillus reuteri RC-14 and Lactobaciullus rhamnosus GR-1
Probiotics are “live microorganisms which when administered in adequate amounts confer a health benefit on the host.”13 Currently, probiotics are not recommended as a standalone treatment for BV. However, supplementation with probiotics appears to be beneficial in managing BV, regardless of concurrent antimicrobial treatment.14
Probiotics are a promising complementary therapy to antimicrobials for the treatment of BV.15-20  Studies have shown that when taken orally, lactobacillus probiotics are safe and can improve the vaginal microbiota.16,21 Lactobacillus reuteri RC-14, which was first isolated from a healthy woman’s urogenital tract, can displace G. vaginalis biofilms in vitro.22Studies combining L. reuteri RC-14 and L. rhamnosus GR-1 show success in colonizing and rebalancing the vaginal microflora.16,21,23 Women treated with a combination of metronidazole, L. rhamnosus GR-1, and L. reuteri RC-14 were more than twice as likely to achieve cure than withantimicrobials alone (88% vs. 40%).15 Another study showed using tinidazole for treating BV was improved when combined with L. rhamnosus GR-1 and L. reuteri RC-14.24 In that study, researchers showed an 87.5% cure rate in probiotic group vs. 50% cure rate in the antibiotic/placebo group.24

​A randomized, double-blind, placebo-controlled trial (RCT) in postmenopausal women with L. rhamnosus GR-1 and L. reuteri RC-14 as a standalone preventative therapy resulted in a shift from “indeterminate” to “normal” vaginal microbiota in 60% of the women in the probiotic group vs. 16% of women in the control group.25 Another RCT revealed that L. rhamnosus GR-1 and L. reuteri RC-14 may prevent BV infections in women with HIV.26
So how do these probiotics, which are taken orally, work to help the vaginal microbiome? L. rhamnosus GR-1 and L. reuteri RC-14 can colonize the vagina from the intestinal tract via the perineum.16,27 Lactobacilli weaken biofilms by producing lactic acid, hydrogen peroxide, bacteriocins, and antiadhesive biosurfactants.20 Biosurfactants produced by L. rhamnosus GR-1 and L. reuteri RC-14 work to disrupt the biofilms created by Gardnerella and residing multispecies anaerobes.20 This disruption allows probiotic strains to displace/crowd out pathogenic bacteria.20 L. rhamnosus GR-1 may also positively impact mucosal immunity, allowing the host to defend against pathogenic bacteria through colonization of the gut or vagina or both.16
With the low long-term cure rate of antibiotics in treating BV and the growing threat of antibiotic resistance, the use of probiotics in treating BV should continue to be explored further.

Final thoughts
BV infections can result in devastating physical, reproductive, and emotional health consequences for women and their partners. The high rate of recurrence underlines the need to improve the current standard of care. Finding personalized, effective, long-term solutions to BV requires ingenuity and tenacity. Emerging BV treatments offer clinicians better solutions to help patients stop the revolving door of BV. Liberating women from a cycle of recurring BV is well worth the endeavor.
Citations

1. Zeron Mullins M et al. BASIC study: is intravaginal boric acid non-inferior to metronidazole in symptomatic bacterial vaginosis? Study protocol for a randomized controlled trial. 2015;16(315).
2. Reichman O et al. Boric acid addition to suppressive antimicrobial therapy for recurrent bacterial vaginosis. Sex Transm Dis. 2009;36:732–734.
3. Marrazzo JM et al. Safety and efficacy of a novel vaginal anti-infective, TOL-463, in the treatment of bacterial vaginosis and vulvovaginal candidiasis: a randomized, single-blind, phase 2, controlled trial. Clin Infect Dis. 2019;68(5):803-809.
4. Iavazzo C et al. Boric acid for recurrent vulvovaginal candidiasis: the clinical J Womens Health. 2011;20:1245–1255.
5. Coste I et al. Safety and efficacy of an intravaginal prebiotic gel in the prevention of recurrent bacterial vaginosis: a randomized double-blind study. Obstet Gynecol Int. 2012;2012:147867.
6. Hakimi S et al. The effect of prebiotic vaginal gel with adjuvant oral metronidazole tablets on treatment and recurrence of bacterial vaginosis: a triple-blind randomized controlled study. Arch Gyn Obstet. 2017;297(1):109-116.
7. Mohammadzadeh F et al. Comparing the therapeutic effects of garlic tablet and oral metronidazole on bacterial vaginosis: a randomized controlled clinical trial. Iran Red Crescent Med J. 2014;16(7):e
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10. Petersen EE et al. Efficacy of vitamin C vaginal tablets in the treatment of bacterial vaginosis: a randomised, double blind, placebo controlled clinical trial. Arzneimittelforschung. 2011;61(4):260-265.
11. Swidsinski A et al. Polymicrobial Gardnerella biofilm resists repeated intravaginal antiseptic treatment in a subset of women with bacterial vaginosis: a preliminary report. Arch Gynecol Obstet. 2015;291(3):605-609.
12. Ha YM et al. Inhibitory effects of seaweed extracts on the growth of the vaginal bacterium Gardnerella vaginalis. J Environ Biol. 2014;35(3):537-542.
13. FAO/WHO. Evaluation of health and nutritional properties of powder milk and live lactic acid bacteria. http://www.fao.org/es/ESN/Probio/probio.htm. Accessed March 10, 2022.
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18. Martinez et al. Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial. Can J Microbiol. 55(2):133-138.
19. Hummelen R et al. Deep sequencing of the vaginal microbiota of women with HIV. PLoS One. 2010;58:12078.
20. McMillan et al. Disruption of urogenital biofilms by lactobacilli. Colloids Surf B Biointerfaces. 2011;86(1):58-64.
21. Liu CM et al. Penile microbiota and female partner bacterial vaginosis in Rakai, Uganda. 2015;6:e00589.
22. Saunders S et al. Effect of Lactobacillus challenge on Gardnerella vaginalis biofilms. Colloids Surf B Biointerfaces. 2007;55(2):138-142.
23. Reid G. The scientific basis for probiotic strains of Lactobacillus. Appl Environ Microbiol. 1999;65:3763-766.
24. Martinez et al. Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial. Can J Microbiol. 55(2):133-138.
25. Petricevic L et al. Randomized, double-blind, placebo-controlled study of oral Lactobacilli to improve the vaginal flora of postmenopausal women. Eur J Obstet Gynecol Reprod Biol. 2008;141(1):54-57.
26. Hummelen R et al. Deep sequencing of the vaginal microbiota of women with HIV. PLoS One. 2010;58:12078.
27. Yang S et al. Effect of oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on the vaginal microbiota, cytokines and chemokines in pregnant women. Nutrients. 2020;12(2):368.