A double-blind treatment study of bacterial vaginosis with normal vaginal lactobacilli after an open treatment with vaginal clindamycin ovules. 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. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Therapy of bacterial vaginosis using exogenously-applied Lactobacilli acidophili and a low dose of estriol: a placebo-controlled multicentric clinical trial.
The expected 4-week cure rate after conventional treatment of bacterial vaginosis are only 65-70%. In an attempt to improve the cure rate by adding probiotic lactobacilli we performed a double-blind placebo-controlled study of adjuvant lactobacilli treatment after an open treatment with vaginal clindamycin ovules. Women with bacterial vaginosis as defined by Amsel's criteria were treated with clindamycin ovules. Vaginal smears were collected and analysed according to Nugent's criteria. During the following menstruation period the women used, as an adjuvant treatment, either lactobacilli-prepared tampons or placebo tampons. The lactobacilli tampons were loaded with a mixture of freeze-dried L. fermentum, L. casei var. rhamnosus and L. gasseri. The cure rate was recorded after the second menstruation period. There was no improvement in the cure rate after treatment with lactobacilli-containing tampons compared to placebo tampons; the cure rates as defined by Amsel's criteria were 56% and 62%, respectively, and 55% and 63%, as defined by Nugent's criteria. This is the first study to report cure rates for women with 'intermediate' wet smear ratings according to Nugent's classification and this group had an overall cure rate of 44%. The cure rate of treatment of bacterial vaginosis was not improved by using lactobacilli-prepared tampons for one menstruation. This study enrolled 125 premenopausal women diagnosed with bacterial vaginosis (BV) by presence of vaginal irritation, discharge and 'fishy' odor, and Nugent criteria and detection of sialidase enzyme. The subjects were treated with oral metronidazole (500 mg) twice daily from days 1 to 7, and randomized to receive oral Lactobacillus rhamnosus GR-1 (1 x 10(9)) and Lactobacillus reuteri RC-14 (1 x 10(9)) or placebo twice daily from days 1 to 30. Primary outcome was cure of BV as determined by normal Nugent score, negative sialidase test and no symptoms or signs of BV at day 30. A total of 106 subjects returned for 30-day follow-up, of which 88% were cured in the antibiotic/probiotic group compared to 40% in the antibiotic/placebo group (p<0.001). Of the remaining subjects, 30% subjects in the placebo group and none in the probiotic group had BV, while 30% in the placebo and 12% in the probiotic group fell into the intermediate category based upon Nugent score, sialidase result and clinical findings. High counts of Lactobacillus sp. (>10(5) CFU/ml) were recovered from the vagina of 96% probiotic-treated subjects compared to 53% controls at day 30. In summary, this study showed efficacious use of lactobacilli and antibiotic in the eradication of BV in black African women. Bacterial vaginosis (BV) is particularly common in black women, and in Nigeria it is often caused by Mycoplasma, as well as Atopobium, Prevotella and Gardnerella sp. Antimicrobial metronidazole oral therapy is poorly effective in eradicating the condition and restoring the Lactobacillus microbiota in the vagina. In this study, 40 women diagnosed with BV by discharge, fishy odor, sialidase positive test and Nugent Gram stain scoring, were randomized to receive either two dried capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each night for 5 days, or 0.75% metronidazole gel, applied vaginally twice a day (in the morning and evening). Follow-up at day 6, 15 and 30 showed cure of BV in significantly more probiotic treated subjects (16, 17 and 18/20, respectively) compared to metronidazole treatment (9, 9 and 11/20: P=0.016 at day 6, P=0.002 at day 15 and P=0.056 at day 30). This is the first report of an effective (90%) cure of BV using probiotic lactobacilli. Given the correlation between BV and HIV, and the high risk of the latter in Nigeria, intravaginal use of lactobacilli could provide women with a self-use therapy, similar to over-the-counter anti-yeast medication, for treatment of urogenital infections. The efficacy of vaginal tablets (Gynoflor) containing 50 mg of a lyophilisate of viable, H2O2-producing Lactobacillus acidophilus (at least 10(7) colony forming units/tablet) and 0.03 mg estriol (CAS 50-27-1) for the treatment of bacterial vaginosis (BV) was tested in a multicentric, randomised, placebo-controlled clinical trial with parallel-group design. 32 non-menopausal women with positive diagnoses for BV, including intermediate cases, participated in the trial. Patients were diagnosed using the classical clinical parameters of BV according to Amsel and using microscopic analysis of the Gram-stained vaginal smear. A positive clinical diagnosis of BV required at least 2 of the following 4 clinical criteria to be positive; greyish-white, homogeneous leukorrhea; vaginal pH > 4.5; KOH test for volatile amines; presence of clue cells. Microscopic diagnosis of BV, on the other hand, was obtained if examination of the Gram-stained vaginal smear showed less than 6 lactobacilli per field of view (1000 x magnification). This corresponds to another definition of BV as "lactobacilli deficiency syndrome". The efficacy of the 6-day therapy with 1-2 vaginal tablets daily was evaluated using both clinical and microscopic analysis. Using Amsel's classical clinical parameters of BV, the cure rate (defined as < or = 1 of the 4 clinical criteria positive) two weeks after the start of therapy was 77% in the verum group and 25% in the placebo group. Four weeks after the start of therapy, the cure rate was 88% in the verum group and 22% in the placebo group. At both control examinations, the cure rate for the test group was significantly higher than that for the placebo group (p < 0.05, Fisher's exact test, 2-sided, significance level 0.05). In addition, the trial showed that after 6 days of treatment with the test preparation, the lactobacilli were capable of recolonising the vagina. A significant increase in the number of lactobacilli was observed in the Gram-stained vaginal smear for the patient group treated with the test preparation compared to the placebo patient group (p < 0.05, Fisher's exact test, 2-sided, significance level 0.05), two and four weeks after the start of the 6-day treatment.
The results do not provide sufficient evidence for or against recommending probiotics for the treatment of BV. The metronidazole/probiotic regimen and probiotic/estriol perparation appear promising but well-designed randomized controlled trials with standardized methodologies and larger patient size are needed.