Could Probiotics Be an Option for Treating and Preventing Urogenital Infections?

Gregor Reid, PhD, MBA, Andrew W. Bruce, MD, FRCS

In This Article

Probiotics in Prophylaxis and Treatment of Urogenital Infections

Since the initial clinical observation that there was an association between recurrent urethritis and absence of lactobacilli,[36] we have conducted a number of clinical studies with L rhamnosus GR-1 and L fermentum RC-14 or B-54, which have shown very encouraging results in preventing recurrent UTI.[57,58,59,60,61,62]

Restoration of a normal vaginal flora has been tried by others with some degree of success, as reviewed by Sieber and Dietz.[63] In our studies, the organisms have been given as a vaginal douche in 3 mL skim milk or as a freeze-dried preparation in gelatin capsules. In the former, vaginal application of strains GR-1 and B-54 increased the number of adherent lactobacilli per vaginal epithelial cell from zero to as high as 110.[57] In the latter, strains GR-1 and B-54 stimulated 10-fold increases in vaginal lactobacilli after intravaginal delivery (from 10,000 to 100,000 per swab per mL).[60] More recently, both GR-1 and RC-14 have been detected and found to be associated with an improved vaginal flora after local insertion of the organisms in capsules.[52] With respect to vaginal colonization, strain GR-1 is more commonly recovered in more women and for longer durations than B-54 or RC-14 (manuscript in preparation). However, RC-14 is a preferred complementary strain, as it produces hydrogen peroxide and potent anti-infective biosurfactants, and in some women colonizes better than GR-1.

The clinical outcome of GR-1 and B-54 given as a douche was assessed in a 5-patient pilot study and the result was a significant extension in the time to infection of up to 6 months in 1 patient, compared with less than 1 month before treatment.[57] This was encouraging, but because of the short shelf-life of the preparation, and the patient's desire to not use a douche, further studies were undertaken using freeze-dried organisms in capsules.

For the randomized, double-blind, double-active study involving 55 women taking strain GR-1 and B-54 weekly or twice weekly by vaginal insertion, the outcome measure was a comparison between the UTI rate 1 year before treatment and 1 year after treatment.[60] The mean incidence was reduced by 79%, and all women responded. In the other arm of the study comprising 21 women, vaginal stimulation of the patient's own lactobacilli flora also resulted in a significantly lower infection rate compared with the previous year.

In a further randomized, placebo-controlled study of 64 women, just recently completed, daily oral ingestion of strains GR-1 and RC-14 significantly improved the vaginal flora, lowering the yeast and coliform counts compared with placebo (Reid G, Charbonneau D, Erb J, et al. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial. Manuscript in preparation).

These trials provide strong support for the role of probiotics in the armamentarium of therapies for urogenital infections. The advantage of the douche is that the organisms are active metabolically at the time of insertion, and the milk acts as a substrate for their growth. However, the shelf-life is very short, making it impractical to scale up, and the patients had to use a tampon overnight to retain the fluid upon insertion. The encapsulation method provided an effective way to produce a large number of doses, all with similar viable counts, which remained viable for 12 months under refrigeration. The actual dosage was chosen somewhat arbitrarily to be once per week. In a few patients, twice per week seemed to give better results, likely because their vaginal flora was so highly colonized by pathogens that were not easy to displace. In the future, we would consider a vaginal capsule of GR-1/RC-14, once daily for 3 days, to treat bacterial vaginosis or abnormal vaginal flora, such as when a woman has UTI, then daily oral capsules for maintenance of a healthy vaginal state.

The maintenance approach comes from the recent discovery that Lactobacillus strains GR-1 and RC-14 can be ingested daily, pass through the gut, and ascend from the rectum to colonize the vagina and/or enhance the indigenous vaginal lactobacilli numbers.[62] This first study group comprised 10 women whose flora were abnormal and who had suffered repeated bacterial vaginosis, yeast infections, and/or UTIs. The regimen consisted of ingesting a capsule containing greater than 109 viable GR-1 and RC-14 bacteria each day. In a number of patients with almost never-ending suprapubic and micturition pain, frequency, dysuria, and urgency or vaginal irritation, the symptoms disappeared, and the patients remained healthy for many months following this treatment regimen. There were no failures, but based on our ongoing studies, we would estimate that at least 50%, and up to 90%, of women would have healthier vaginal flora within 1-2 weeks of GR-1/RC-14 therapy.

As almost all women have an abnormal vaginal flora at some point in any given month, whether menstruating or postmenopausal,[38,39] daily oral probiotic intake may prove to be a natural method for women to restore and maintain urogenital as well as intestinal health. However, oral therapy for symptomatic bacterial vaginosis is less likely to be effective, unless it follows either antibiotic treatment or 3 nightly treatments with GR-1/RC-14 vaginal capsules to displace the Gardnerella pathogens.

The concept of using lactobacilli (ie, probiotic therapy) to treat candidiasis is not new, and a small study with L rhamnosus GG suggested that it could be effective.[64] However, only a few strains of lactobacilli, including GR-1 and RC-14, inhibit yeast growth or detach pathogens from surfaces. Having said that, effective treatment of symptomatic yeast vaginitis with probiotics seems unlikely, and more studies are warranted before this approach can be recommended. Rather, the eradication of the yeast by antifungals followed by application of probiotics to restore a normal bacterial flora constitutes a more effective means to prevent recurrence of candidiasis.


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