Lactobacilli for the Treatment of Urogenital Infections
Lactobacilli for the Treatment of Urogenital Infections
March 2000; Volume 2: 17-19
By Gregor Reid, PhD
Probiotics, or bacteriotherapy, is the use of good "bugs" to fight bad ones. Until recently, there was a lack of good published data on probiotics, but this is changing. Lactobacilli may have multiple modes of action, and different strains may act differently. (See Alternative Therapies in Women’s Health, November 1999, pp. 91-94.)
Mechanisms of action for probiotics may include colonization resistance; the production of antimicrobial substances including lactic acid and hydrogen peroxide; competition for nutrients; and competitive inhibition for bacterial adhesion sites.1
A review of placebo-controlled trials of biotherapeutic agents between 1966 and 1995 concluded that there is evidence to support the use of various organisms to prevent antibiotic-associated diarrhea (Lactobacilli casei GG, Bifidobacterium longum, Saccharomyces boulardii) and acute infantile diarrhea (Bifidobacterium bifidum with Streptococcus thermophilus), and to treat recurrent Clostridium difficile infection (Saccharomyces boulardii) and other diarrheal diseases.1 The reviewers noted that there is limited evidence for lactobacillus in the prevention of candidal vaginitis.1
Renal Failure
Probiotics have been tested in patients with renal failure. Nineteen patients with end-stage kidney disease and small bowel bacterial overgrowth were treated with L. acidophilus NCFM and BG2F04 in freeze-dried, enteric-coated capsules.2 Each capsule contained 80 mg of freeze-dried organisms containing 1010-1011 colony-forming units per gram. Patients were given one capsule twice daily for an average of 67 days. The capsules released the organisms into the small bowel and significantly decreased both dimethylamine toxin and the carcinogen nitrosodimethylamine (products of gut bacteri). Increased caloric intake and weight gain were demonstrated. In this very ill group of patients, such probiotic therapy has the potential to make a major contribution to well being.
UTIs and Vaginal Infections
There is scant work to date on treating or preventing urogenital infections. Strain L. rhamnosus GR-1 has been shown to colonize the vagina for at least seven weeks after a single implantation.3 In one study, 55 women with a history of recurrent UTI were randomized to a capsule containing >109 viable organisms GR-1 and L. fermentum B-54 or a capsule containing skim milk lactobacillus growth factor (LGF). Each capsule was inserted vaginally once weekly. Enrolled subjects had experienced a mean of six UTIs in the previous year. Both treatment groups experienced a decrease in recurrent UTI (symptomatic or asymptomatic); however, there were no significant differences between groups. Forty-four subjects completed the year-long study. Compared to the previous 12 months, there was a 79% reduction in UTIs among subjects given lactobacilli and an 83% reduction among those given LGF.4 It bears noting that although the LGF was shown to dramatically stimulate the growth of indigenous lactobacilli, this treatment would only be effective in women with lactobacilli present in the vaginal flora. Many patients with recurrent UTI do not have a normal flora that a prebiotic (a growth stimulant for probiotic organisms) could stimulate. The above trial was not placebo-controlled; a randomized, placebo-controlled trial is planned.
Conventional UTI prophylaxis is daily treatment with antibiotics. Given the doubling of bacterial resistance to trimethoprim/sulfamethoxazole, the commonly prescribed antibiotics for UTI prophylaxis,5 and the side effects of antibiotics, probiotics seem to be a good alternative. A study that directly compares lactobacilli to antibiotics is needed to demonstrate whether the probiotic remedy is truly a good alternative.
Vaginitis
In one crossover study, daily ingestion of 8 oz yogurt containing >108 organisms/ml of a hydrogen-peroxide producing strain of L. acidophilus for six months was successful in reducing episodes of vulvovaginal candidiasis (the number of infections in six months was 2.54 +/-1.66 in the no-yogurt control phase and 0.38 +/-0.51 during the lactobacilli phase). The mean number of colonizations with Candida was also significantly reduced from 0.23 +/-2.17 to 0.84 +/-0.9 during the yogurt phase.6
There are several problems with this study. Too few patients (13/33) completed the crossover (a number of women refused to enter the no-yogurt phase); no characterization of the strain is provided; and there was no identification of lactobacilli in vaginal samples to see whether the implanted lactobacilli had taken up residence.
Studies are underway in Pittsburgh using vaginally administered L. crispatus CTV05 to reduce the risk of bacterial vaginosis (BV), and although preliminary findings are encouraging, final outcomes are pending. Successful colonization of the vagina by this and other strains could be particularly useful in pregnancy, where BV is a risk factor for preterm labor7 and where antibiotic options are more limited.
Can Oral Treatment Work?
Uropathogens primarily reach the vagina and bladder from the intestine. There is some evidence that lactobacilli also follow this path to the vagina. In the Hilton study, there was a significant relationship between the presence of L. acidophilus in the rectum and the vagina. It is unclear whether the lactobacilli exerts its main effect against pathogens when these harmful organisms are in the intestine or in the vagina.
In one patient with chronic enterococcal cystitis treated with L. rhamnosus GR-1 and L. fermentum RC-14 (which possesses potent anti-uropathogen adhesion proteins), the enterococci were eradicated from the bladder and depleted down to a few colonies in the vagina (G Reid, unpublished data, January 2000). This finding is exciting as the lactobacilli therapy correlated with cure of bacteriuria and improved the patient’s well-being for the first time in four years. Of course, this is only one case and further studies are needed.
Attention to the diversity and interactions of microbial flora may increase the chances of successful treatment of recurrent urogenital infections. Prophylactic antibiotics are successful only as long as the therapy is used because antibiotics kill bacteria as they enter the bladder. Ideally, antibiotics should be chosen to be very selective for the uropathogen, whether E. coli or enterococci in the case of UTI or anaerobic gram-negatives in the case of BV. Using antibiotics targeted at a specific organism will disrupt normal flora less. Combined therapy with probiotics may also be beneficial.
In Europe, probiotics are widely available in oral forms, including yogurt, milk-based drinks, and freeze-dried dietary supplements, but very few contain strains with proven, published efficacy or mechanisms of action. Indeed, a recent report exposed many so-called probiotic products as being unreliable.8 A select group of lactobacilli (including GG, MM53, NCFM, CRL431 and perhaps LA1 [an organism which keeps getting renamed to LC1, LJ1 and is now known in some circles as LA5]) possesses properties that could make them good probiotic agents.4 Although no probiotic product is yet available to effectively prevent or treat urogenital infections, ongoing research on well-characterized and properly selected lactobacilli suggests that breakthroughs are on the horizon.
Dr. Reid is Associate Scientific Director of the Lawson Research Institute and Professor of Microbiology and Immunology at the University of Western Ontario, London, ON, Canada. Dr. Reid has a financial interest in Urex Biotech Inc., a company with patents on lactobacilli probiotics.
References
1. Elmer GW, et al. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA 1996;275: 870-876.
2. Dunn SR, et al. Effect of oral administration of freeze-dried Lactobacillus acidophilus on small bowel bacterial overgrowth in patients with end stage kidney disease: Reducing uremic toxins and improving nutrition. Int Dairy J 1998;8:545-553.
3. Reid G, et al. Implantation of Lactobacillus casei var rhamnosus into vagina. Lancet 1994;344:1229.
4. Reid G, et al. Instillation of Lactobacillus and stimulation of indigenous organisms to prevent recurrence of urinary tract infections. Microecol Ther 1995;23:32-45.
5. Gupta K, et al. Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women. JAMA 1999;281:736-738.
6. Hilton E, et al. Ingestion of yogurt containing Lactobacillus acidophilus as prophylaxis for candidal vaginitis. Ann Intern Med 1992;116:353-357.
7. Hillier SL, et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. N Engl J Med 1995;333:1737-1742.
8. Hamilton-Miller JM, et al. Public health issues arising from microbiological and labelling quality of foods and supplements containing probiotic microorganisms. Public Health Nutr 1999;2:223-229.
Funding of Reviewed Studies
Reference 1: All authors are employees or consultants for Biocodex, which manufactures one of the agents discussed in the article. Reference 2: the California Dairy Research Foundation and the North Carolina Dairy Research Foundation. Reference 3: not sponsored. Reference 4: the Ontario Ministry of Health. References 5-8: funding sources not available.
March 2000; Volume 2: 17-19
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