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Lactobacillus Rhamnosus GR-1 and L. Reuteri RC-14 for genitourinary infections in women.

Lactobacilli are a normal component of the urogenital flora of healthy women. These "friendly" bacteria (usually called probiotics) may help prevent genitourinary infections (i.e., urinary tract infections, bacterial vaginosis, and candidiasis) and increase the efficacy of conventional therapy in women suffering from such infections. Probiotics work by several different mechanisms, including competing with pathogenic organisms for nutrients and for binding sites on uroepithelial cells, and producing substances that kill or inhibit the growth of pathogens.

The bacterial flora of healthy people differs substantially in different parts of the body. Probiotic strains may also differ in their capacity to colonize, and provide protection to, different areas of the body. For example, Lactobacillus rhamnosus GG, which colonizes and has beneficial effects on gastrointestinal health, does not appear to be particularly effective as a probiotic for the genitourinary system. (1)

Two Lactobacillus strains--L. rhamnosus GR-1 and. L. reuteri RC-14 (formerly known as L. fermentum RC-14)-have been found to be useful for preventing and treating various types of genitourinary infections in women. These organisms, originally isolated from the distal urethra or vagina of healthy women, are more effective than other Lactobacillus strains at colonizing the vaginal mucosa, adhering to uroepithelial cells, competing against pathogenic organisms, and producing compounds that inhibit the growth of urogenital pathogens (including Candida albicans). (2-5) L. rhamnosus GR-1 and L. reuteri RC-14 also disrupt the biofilms produced by common urogenital pathogens, and thereby interfere with one of the survival mechanisms of these pathogens. (6)

L. rhamnosus GR-1 and L. reuteri RC-14 have been shown to exert beneficial effects on the genitourinary system after oral administration. These organisms survive passage through the gastrointestinal tract and then apparently migrate to and colonize the genitourinary tract. (7) The fact that it is not necessary to administer L. rhamnosus G R-1 and L. reuteri RC-14 intravaginally is advantageous with respect to convenience and patient compliance.

Urinary Tract Infections

In a double-blind trial, 252 postmenopausal women (mean age, 64 years) with at least 3 self-reported symptomatic urinary tract infections (UTIs) in the previous year were randomly assigned to receive antibiotic prophylaxis (480 mg of trimethoprim-sulfamethoxazole once a day) or oral capsules containing [10.sup.9] colony-forming units of L. rhamnosus GR-1 and L. reuteri RC-14 twice a day for 12 months. During the trial, as compared with the year before the trial, the number of UTI episodes fell by 58.5% in the antibiotics group and by 51.4% in the probiotics group (difference not statistically significant). In the antibiotics group, resistance of uropathogenic Escherichia coil to trimethoprim-sulfamethoxazole and to amoxicillin increased from 20% to 40% at baseline to 80% to 95% after 1 month of treatment. In contrast, resistance to these antibiotics did not occur during probiotic treatment. (8)

Thus, the combination of L. rhamnosus GR-1 and L. reciteri RC-14 was nearly as effective as antibiotics for preventing UTI recurrences and, unlike trimethoprim-sulfamethoxazole, did not lead to antibiotic resistance.

Bacterial Vaginosis

One hundred twenty-five women with bacterial vaginosis were treated with oral metronidazole (500 mg twice a day for 7 days). They were also randomly assigned to receive, in double-blind fashion, 1 capsule twice of day of L. rhamnosus GR-1 and L. reciter! RC-14 or placebo for 30 days, beginning with the start of metronidazole therapy. Each capsule contained [10.sup.9] viable cells of both strains. Cure of bacterial vaginosis was defined as a normal Nugent score, a negative sialidase test, and no symptoms or signs at day 30. Among the 106 patients who completed the trial, the cure rate was 88% in the probiotics group and 40% in the placebo group (p ----- 0.001). (9)

Sixty-four women with bacterial vaginosis were treated with a single 2 g dose of the antibiotic tinidazole and were randomly assigned to receive, in double-blind fashion, 2 oral capsules containing L. rhamnosus GR-1 and L. reciteri RC-14 every morning for 4 weeks, starting on the day tinidazole was given. After 4 weeks, the cure rate was significantly higher in the probiotics group than in the placebo group (87.5% vs. 50.0%; p=0.001). (10)

Vulvovaginal Candidiasis

Fifty-five women (mean age, 28 years) with vulvovaginal candidiasis were given a single 150 mg dose of fluconazole and were randomly assigned to receive, in double-blind fashion, 2 capsules each morning containing L. rhamnosus GR-1 and L. reuteri RC-14 (2 x [10.sup.9] viable cells per day of each strain) or placebo for 4 weeks, starting on the day of fluconazole use. After 4 weeks, the proportion of women who were symptom free (90% vs. 65%; p = 0.3) and the proportion of women who had a negative culture for Candida (90% vs. 61%; p ----- 0.02) was significantly higher in the active-treatment group than in the placebo group. (11)

Improving the Vaginal Flora in Postmenopausal Women

In premenopausal women, estrogen encourages vaginal colonization with lactobacilli. The decline in estrogen levels that occurs with menopause is associated with a decrease in lactobacilli, increased colonization with enterobacteria, and an increased incidence of urinary tract infections.

Seventy-two postmenopausal women (mean age, 57.6 years) with abnormal vaginal flora (i.e., intermediate flora; Nugent scores of 4-6) were randomly assigned to receive, in double-blind fashion, 2.5 x [10.sup.9] viable cells each of L. rhamnosus GR-1 and L. reuteri RC-14 or placebo once a day for 14 days. The proportion of women who showed a reduction (improvement) in the Nugent score of at least 2 grades was significantly greater in the probiotics group than in the placebo group (60% vs. 16%; p = 0.0001). The median Nugent score decreased by 3 grades in the probiotics group and did not change in the placebo group (p = 0.0001 for the difference in the change between groups). (12) These results indicate that treatment with this probiotic combination restored the vaginal flora toward normal in postmenopausal women.

Conclusion

Oral administration of the combination of L. rhamnosus GR-1 and L. reuteri RC-14 has been found effective for the prevention of recurrent urinary tract infections in postmenopausal women. These probiotic strains also increased the cure rate in women with bacterial vaginosis or vulvovaginal candidiasis, when given as an adjunct to conventional therapy. In addition, L. rhamnosus GR-1 and L. reuteri RC-14 restored the vaginal flora toward normal in postmenopausal women.

Notes

(1.) Reid G, Bruce AW. Selection of Lactobacillus strains for urogenital probiotic applications. l Infect Dis. 2001;183(Suppl 1)577-580.

(2.) Gardiner GE et al. Persistence of Lactobacillus fermentum RC-14 and Lactobacillus rhamnosus GR-1 but not L. rhamnosus GG in the human vagina as demonstrated by randomly amplified polymorphic DNA. Clin Diagn Lab Immunol. 2002;9:92-96.

(3.) Reid G, Bruce AW. Selection of lactobacillus strains for urogenital probiotic applications. 1 Infect Dis. 2001;183(Suppl 1):577-S80.

(4.) Reid G. Probiotic agents to protect the urogenital tract against infection. Am 1 Clin Nutr. 2001; 73(Suppl):4375-4435.

(5.) Kohler GA et al. Probiotic interference of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 with the opportunistic fungal pathogen Candida albicans. Infect Dis Obstet Gynecol. 2012;2012:636474.

(6.) McMillan A, et al. Disruption of urogenital biofilms by lactobacilli. Colloids Surf B Biointerfaces. 2011;86:58-64.

(7.) Reid G, Bruce AW, Fraser N, Heinemann C, Owen J, Henning B. Oral probiotics can resolve urogenital infections. FEMS immunol Med Microbial. 2001;30:49-52.

(8.) Beerepoot MAJ, ter Riet G, Nys S, et al. Lactobacilli vs antibiotics to prevent urinary tract infection. A randomized, double-blind, noninferiority trial in postmenopausal women. Arch Intern Med. 2012;172:704-712.

(9.) 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.

(10.) Martinez RCR et al. Improved cure of bacterial vaginosis with single dose of tinidazote (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial. Can 1 Microbial. 2009;55:133138.

(11.) Martinez RCR, et al. Improved treatment of vulvovaginal candidiasis with fluconazole plus probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Lett Appl Microbial. 2009;48:269-274.

(12.) Petricevic L et al. Randomized, double-blind, placebo-controlled study of oral lactobacilli to improve the vaginal flora of postmenopausal women. Fur I Obstet Gynecol Reprod Biol. 2008;141:54-57.

Disclosure

Dr. Gaby receives a royalty for sales of a product that contains L. rhamnosus GR-1 and L. reuteri RC-14.
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Title Annotation:Editorial
Author:Gaby, Alan R.
Publication:Townsend Letter
Date:Feb 1, 2013
Words:1397
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