title: Efficacy of Oral Metronidazole with Vaginal Clindamycin or Vaginal Probiotic for Bacterial Vaginosis: Randomised Placebo-Controlled Double-Blind Trial Phase 2a Study Assessing Colonization Efficiency, Safety, and Acceptability of Lactobacillus crispatus CTV-05 in Women With Bacterial Vaginosis Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. 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. The use of Lactobacillus rhamnosus in the therapy of bacterial vaginosis. Evaluation of clinical efficacy in a population of 40 women treated for 24 months Effectiveness of vaginal tablets containing lactobacilli versus pH tablets on vaginal health and inflammatory cytokines: a randomized, double-blind study Effectiveness of vaginal administration of Lactobacillus rhamnosus following conventional metronidazole therapy: how to lower the rate of bacterial vaginosis recurrences. Can Lactobacillus fermentum LF10 and Lactobacillus acidophilus LA02 in a Slow-release Vaginal Product be Useful for Prevention of Recurrent Vulvovaginal Candidiasis?: A Clinical Study Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. Effectiveness of the Two Microorganisms Lactobacillus fermentum LF15 and Lactobacillus plantarum LP01, Formulated in Slow-release Vaginal Tablets, in Women Affected by Bacterial Vaginosis: A Pilot Study Are probiotics safe for use during pregnancy and lactation? Probiotics enhance the clearance of human papillomavirus-related cervical lesions: a prospective controlled pilot study Lactic acid bacteria colonization and clinical outcome after probiotic supplementation in conventionally treated bacterial vaginosis and vulvovaginal candidiasis.
abstract: Background To determine if oral metronidazole ( MTZ-400 mg bid ) with 2 % vaginal clindamycin-cream ( Clind ) or a Lactobacillus acidophilus vaginal-probiotic containing oestriol ( Prob ) reduces 6-month bacterial vaginosis ( BV ) recurrence . Methods Double-blind placebo-controlled parallel-group single-site study with balanced r and omization ( 1∶1∶1 ) conducted at Melbourne Sexual Health Centre , Australia . Participants with symptomatic BV [ Nugent Score ( NS ) = 7–10 or ≥3 Amsel 's criteria and NS = 4–10 ] , were r and omly allocated to MTZ-Clind , MTZ-Prob or MTZ-Placebo and assessed at 1,2,3 and 6 months . MTZ and Clind were administered for 7 days and Prob and Placebo for 12 days . Primary outcome was BV recurrence ( NS of 7–10 ) on self-collected vaginal-swabs over 6-months . Cumulative BV recurrence rates were compared between groups by Chi-squared statistics . Kaplan-Meier , log rank and Cox regression analyses were used to compare time until and risk of BV recurrence between groups . Results 450 18–50 year old females were r and omized and 408 ( 91 % ) , equally distributed between groups , provided ≥1 NS post-r and omization and were included in analyses ; 42 ( 9 % ) participants with no post-r and omization data were excluded . Six-month retention rates were 78 % ( n = 351 ) . One-month BV recurrence ( NS 7–10 ) rates were 3.6 % ( 5/140 ) , 6.8 % ( 9/133 ) and 9.6 % ( 13/135 ) in the MTZ-Clind , MTZ-Prob and MTZ-Placebo groups respectively , p = 0.13 . Hazard ratios ( HR ) for BV recurrence at one-month , adjusted for adherence to vaginal therapy , were 0.43 ( 95%CI 0.15–1.22 ) and 0.75 ( 95 % CI 0.32–1.76 ) in the MTZ-Clind and MTZ-Prob groups compared to MTZ-Plac respectively . Cumulative 6-month BV recurrence was 28.2 % ; ( 95%CI 24.0–32.7 % ) with no difference between groups , p = 0.82 ; HRs for 6-month BV recurrence for MTZ-Clind and MTZ-Prob compared to MTZ-Plac , adjusted for adherence to vaginal therapy were 1.09(95 % CI = 0.70–1.70 ) and 1.03(95 % CI = 0.65–1.63 ) , respectively . No serious adverse events occurred . Conclusion Combining the recommended first line therapies of oral metronidazole and vaginal clindamycin , or oral metronidazole with an extended-course of a commercially available vaginal-L.acidophilus probiotic , does not reduce BV recurrence . Trial Registration ANZCTR.org.au Background : Bacterial vaginosis ( BV ) is a common vaginal infection caused by a lack of endogenous lactobacilli and overgrowth of pathogens that frequently recurs following antibiotic treatment . Methods : A phase 2a study assessed colonization efficiency , safety , tolerability , and acceptability of Lactobacillus crispatus CTV-05 ( LACTIN-V ) administered by a vaginal applicator . Twenty-four women with BV were r and omized in a 3:1 ratio of active product to placebo . Participants used LACTIN-V at 2 × 109 colony-forming units (cfu)/dose or placebo for 5 initial consecutive days , followed by a weekly application over 2 weeks . They returned for follow-up on Days 10 and 28 . Results : Sixty-one percent of the 18 women r and omized to the LACTIN-V group were colonized with L. crispatus CTV-05 at Day 10 or Day 28 . Among LACTIN-V users with complete adherence to the study regimen , 78 % were colonized at Day 10 or Day 28 . Of the 120 adverse events ( AEs ) that occurred , 108 ( 90 % ) and 12 ( 10 % ) were of mild and moderate severity , respectively . AEs were evenly distributed between the LACTIN-V and placebo group . Of the total AEs , 93 ( 78 % ) were genitourinary in origin . The most common genitourinary AEs included vaginal discharge ( 46 % ) , abdominal pain ( 46 % ) , dysuria ( 21 % ) , pollakiuria ( 21 % ) , vaginal odor ( 21 % ) , and genital pruritus ( 17 % ) . No grade 3 or 4 AEs or serious AEs occurred and no deep epithelial disruption was seen during colposcopic evaluation . The product was well tolerated and accepted . Conclusions : LACTIN-V colonized well , and was safe and acceptable in women treated for BV BACKGROUND Urinary tract infections ( UTIs ) are common among women and frequently recur . Depletion of vaginal lactobacilli is associated with UTI risk , which suggests that repletion may be beneficial . We conducted a double-blind placebo-controlled trial of a Lactobacillus crispatus intravaginal suppository probiotic ( Lactin-V ; Osel ) for prevention of recurrent UTI in premenopausal women . METHODS One hundred young women with a history of recurrent UTI received antimicrobials for acute UTI and then were r and omized to receive either Lactin-V or placebo daily for 5 d , then once weekly for 10 weeks . Participants were followed up at 1 week and 10 weeks after intervention and for UTIs ; urine sample s for culture and vaginal swabs for real-time quantitative 16S ribosomal RNA gene polymerase chain reaction for L. crispatus were collected . RESULTS Recurrent UTI occurred in 7/48 15 % of women receiving Lactin-V compared with 13/48 27 % of women receiving placebo ( relative risk [ RR ] , .5 ; 95 % confidence interval , .2 - 1.2 ) . High-level vaginal colonization with L. crispatus ( ≥10(6 ) 16S RNA gene copies per swab ) throughout follow-up was associated with a significant reduction in recurrent UTI only for Lactin-V ( RR for Lactin-V , .07 ; RR for placebo , 1.1 ; P < .01 ) . CONCLUSIONS Lactin-V after treatment for cystitis is associated with a reduction in recurrent UTI . Larger efficacy trials of this novel preventive method for recurrent UTI are warranted . CLINICAL TRIALS REGISTRATION . NCT00305227 Bacterial vaginosis ( BV ) is the most prevalent vaginal infection worldwide and is characterized by depletion of the indigenous lactobacilli . Antimicrobial therapy is often ineffective . We hypothesized that probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 might provide an adjunct to antimicrobial treatment and improve cure rates .  Sixty-four Brazilian women diagnosed with BV were r and omly assigned to receive a single dose of tinidazole ( 2 g ) supplemented with either 2 placebo capsules or 2 capsules containing L. rhamnosus GR-1 and L. reuteri RC-14 every morning for the following 4 weeks . At the end of treatment ( day 28 ) , the probiotic group had a significantly higher cure rate of BV ( 87.5 % ) than the placebo group ( 50.0 % ) ( p = 0.001 ) . In addition , according to the Gram-stain Nugent score , more women were assessed with " normal " vaginal microbiota in the probiotic group ( 75.0 % vs. 34.4 % in the placebo group ; p = 0.011 ) . This study shows that probiotic lactobacilli can provide benefits to women being treated with antibiotics for an infectious condition Background Bacterial vaginosis ( BV ) is the most prevalent vaginal disorder in adult women worldwide . A number of clinical studies indicate that re-establishment of the physiological ecosystem by re-colonization of vaginal mucosa by lactobacilli may be an effective therapy for BV both after initial antimicrobial therapy or when given alone . A vaginal pH < 4.5 is considered physiological and its measurement has been reported as an objective parameter , very sensitive to alterations of vaginal microflora and correlated with clinical ly relevant BV . Objective The aims of this work were to assess the effectiveness of a long-term ( 24 months ) intravaginal treatment with Lactobacillus rhamnosus ( NORMOGIN ® ) on the vaginal pH and on the clinical symptoms in a group of 40 women affected by BV diagnosed by the Amsel criteria . Method A prospect i ve open clinical trial was performed in 40 consecutive cases evaluated for B.V. by the Amsel criteria . Results Vaginal pH was above the physiological value of 4.5 in 36 out of 40 patients at the first visit . It returned under 4.5 value in 24/40 and 32/40 women after 12 and 24 months of treatment , respectively . pH values were significantly decreased at 12 month treatment ( P < 0.001 ) and further reduction in pH values was found at 24 months of treatment ( P < 0.02 vs. 12 months ) . The gradual return to a vaginal physiological pH was associated with a reduction of the intensity of symptoms as shown by the decrease in the symptoms score . Conclusions The present study supports the use of pH measurement for sensitive , objective , and simple therapy follow-up in women with BV and shows that long-term administration of vaginal tablets containing Lactobacillus rhamnosus represents an effective and safe treatment for restoring the physiological vaginal pH and controlling BV symptoms Abstract The purpose of this study was to evaluate the effectiveness of lactobacilli on vaginal health and proinflammatory cytokines . Sixty-seven patients with bacterial vaginosis ( BV ) , 50 with intermediate flora and 42 with normal vaginal flora were enrolled in this double-blind study . The subjects were r and omized to receive probiotic lactobacilli vaginal tablets ( L. brevis CD2 , L. salivarius subsp . salicinius , L. plantarum ) or the vaginal pH tablet ( active comparator ) . Cervico-vaginal lavage was collected to measure the concentrations of IL-1β , TNFα and IL-6 by ELISA . Neutral sphingomyelinase activity was also quantified in both arms before and after treatment . The probiotic vaginal tablet was well tolerated and no side effects were reported . The study demonstrated a cure rate of nearly 80 % ; i.e. , 32 % of the women could restore normal vaginal flora and 47 % had improved Nugent score , whereas 20 % of the subjects did not clear BV in the first follow-up ( after 8 days treatment ) . The pH tablet containing pH lowering compounds induced resolution of BV and restoration of normal vaginal flora in 74 % and 26 % , respectively . The lactobacilli tablet was found to be better than the pH tablet in preventing BV in healthy subjects . A significant reduction in IL-1β and IL-6 vaginal cytokines was observed after treatment with lactobacilli , while the active comparator did not have any effect on local proinflammatory cytokines . Vaginal neutral sphingomyelinase activity was not modified in either group . Vaginal tablets containing lactobacilli can cure BV and reduce vaginal inflammatory response Eighty-four patients with bacterial vaginosis diagnosed according to Amsel 's criteria were r and omized to receive either oral metronidazole 500 mg twice a day for seven days , or one vaginal tablet containing freeze-dried Lactobacillus rhamnosus once a week at bedtime for two months starting one week after the last antibiotic administration . Followup was performed at days 30 , 90 and 180 . Chi-squared analysis showed a significant difference between the two treatment groups at day 90 ( P = 0.05 ) . Safe and effective long-term vaginal administration of Lactobacillus rhamnosus appears to be a useful complementary approach in the management of bacterial vaginosis Objective : To assess the effectiveness of the association of 2 specific strains , Lactobacillus fermentum LF10 ( DSM 19187 ) and Lactobacillus acidophilus LA02 ( DSM 21717 ) , specifically formulated in slow-release effervescent tablets , in patients with recurrent vulvovaginal c and idiasis . Study Design : The study was a clinical trial of 58 women diagnosed with recurrent VVC ( ≥4 culture-confirmed episodes in a 12-mo period ) . All patients were given 200 mg of fluconazole orally as an induction dose for 3 alternate days during the first treatment week . Afterward , the patients were given a new product formulated in slow-release vaginal tablets containing at least 0.4 billion live cells of each of lactobacillus L. fermentum LF10 and L. acidophilus LA02 ( first phase of the prophylactic period ) , on alternate days for 10 consecutive nights . Patients who were still free of symptoms were given 1 vaginal tablet every week for the next 10 weeks ( second phase of the prophylactic period ) . Patients asymptomatic after the total duration of the observation phase ( 7 mo ) were considered as responders . Results : During the second 10-week prophylactic phase , 49 of 57 ( 86.0 % ) patients remained free of clinical recurrence , whereas symptomatic VVC occurred in 8 patients ( 14.0 % ) . During the 7-month follow-up , 42 patients of 49 ( 85.7 % ) were symptom free at the end of the protocol , whereas clinical recurrences occurred in 7 women ( 14.3 % ) . Overall , 42 of 58 women enrolled in the study ( 72.4 % ) experienced no clinical recurrence throughout the 7-month observation phase ( responders ) . Conclusions : This study strengthens the evidence supporting the use of specific lactobacilli with well-demonstrated activities associated with the creation and maintenance of a vaginal biofilm that hinders the persistence of an infection caused by C and ida Urogenital infections afflict an estimated one billion people each year . The size of this problem and the increased prevalence of multi-drug resistant pathogens make it imperative that alternative remedies be found . A r and omized , placebo-controlled trial of 64 healthy women given daily oral capsules of Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 for 60 days showed no adverse effects . Microscopy analysis showed restoration from asymptomatic bacterial vaginosis microflora to a normal lactobacilli colonized microflora in 37 % women during lactobacilli treatment compared to 13 % on placebo ( P=0.02 ) . Lactobacilli were detected in more women in the lactobacilli-treated group than in the placebo group at 28 day ( P=0.08 ) and 60 day ( P=0.05 ) test points . Culture findings confirmed a significant increase in vaginal lactobacilli at day 28 and 60 , a significant depletion in yeast at day 28 and a significant reduction in coliforms at day 28 , 60 and 90 for lactobacilli-treated subjects versus controls . The combination of probiotic L. rhamnosus GR-1 and L. fermentum RC-14 is not only safe for daily use in healthy women , but it can reduce colonization of the vagina by potential pathogenic bacteria and yeast Background : Bacterial vaginosis ( BV ) is the most common reason for abnormal vaginal discharge in reproductive-age women and one of its most important causative agents is the gram-variable bacterium Gardnerella vaginalis . BV is not accompanied by significant local inflammation , whereas the “ fishy odor ” test is always positive . In contrast , aerobic vaginitis ( AV ) is predominantly associated with Escherichia coli , but Streptococcus agalactiae and Staphylococcus aureus are also involved . St and ard treatment of BV consists of oral or intravaginal antibiotics , although these are unable to spontaneously restore normal flora characterized by a high concentration of lactobacilli . The main limitation is the inability to offer a long-term defensive barrier , thus facilitating relapses and recurrences . This study was undertaken firstly to assess the ability of selected lactobacilli to in vitro antagonize G. vaginalis to determine an association with a strain able to inhibit E. coli , thus identifying a possible use in AV . The second step of the study was to conduct a human pilot trial in women affected by BV using an association of the most promising and active bacteria . Material s and Methods : For this purpose , neutralized supernatants of individual lactobacilli were tested at percentages ranging from 0.5 % to 4 % to determine their ability to hinder the growth of G. vaginalis American Type Culture Collection 10231 . The bacterium that was able to exert the strongest inhibition was subsequently tested with Lactobacillus plantarum LP01 in a human intervention , placebo-controlled , pilot trial involving 34 female subjects ( aged between 18 and 50 , mean 34.7±8.9 , no menopausal women ) diagnosed with BV . The 2 microorganisms Lactobacillus fermentum LF15 ( DSM 26955 ) and L. plantarum LP01 ( LMG P-21021 ) were delivered to the vagina by means of slow-release vaginal tablets , also containing 50 mg of tara gum . The amount of each strain was 400 million live cells per dose . The women were instructed to apply a vaginal tablet once a day for 7 consecutive nights , followed by 1 tablet every 3 nights for a further 3-week application ( acute phase ) and , finally , 1 tablet per week to maintain a long-term vaginal colonization against possible recurrences . A clinical examination was performed and the Nugent score was quantified for each patient at enrollment ( d0 ) , after 28 days ( d28 ) , and at the end of the second month of relapse prevention ( d56 ) . A statistical comparison was made between d28 , or d56 , and d0 , and between d56 and d28 to quantify the efficacy against possible recurrences . Results : L. fermentum LF15 showed the strongest in vitro inhibitory activity towards G. vaginalis American Type Culture Collection ( ATCC ) 10231 after both 24 and 48 hours . In the human trial , the 2 lactobacilli selected , namely L. fermentum LF15 and L. plantarum LP01 , significantly reduced the Nugent score below the threshold of 7 after 28 days in 22 patients of 24 in the active group ( 91.7 % , P<0.001 ) . Eight women ( 33.3 % ) recorded a Nugent score between 4 and 6 , evidence of an intermediate situation , whereas the remaining 14 ( 58.3 % ) showed a score < 4 , therefore suggesting the restoration of physiological vaginal microbiota . At the end of the second month , only 4 women registered a Nugent score > 7 , definable as BV ( 16.7 % , P=0.065 compared with d28 ) . In the placebo group , no significant differences were recorded at any time . Conclusions : BV , also known as vaginal bacteriosis is the most common cause of vaginal infection in women of childbearing age . Furthermore , BV is often asymptomatic as about 50 % of women with this condition have no symptoms at all and the prevalence rate in apparently healthy women is around 10 % . This study suggests the ability of the 2 strains L. fermentum LF15 and L. plantarum LP01 to counteract acute Gardnerella infections effectively and significantly improve the related uncomfortable symptoms in a very high percentage of women . This could be partially attributed to the presence of tara gum , which is able to create a mechanical barrier against Gardnerella on the surface of vaginal mucosa as a primary mechanism . Furthermore , long-term physiological protection seems to be established , thanks to the integration of the 2 lactobacilli into the vaginal microbiota and to their adhesion to the epithelial cells of the mucosa . In the light of the additional in vitro inhibitory activity against E. coli , their prospect i ve use in AV could also prove interesting QUESTION There has been a great deal of discussion in both the medical and lay literature about the use of probiotics to improve general health . Subsequently , pregnant women have been asking me if probiotics used for treating conditions such as bacterial vaginosis and diarrhea are safe to use during pregnancy and lactation . ANSWER Current data suggest that probiotic supplementation is rarely systemically absorbed when used by healthy individuals . One meta- analysis and several r and omized controlled trials conducted with women during the third trimester of pregnancy did not report an increase in adverse fetal outcomes . There have been no published studies addressing Saccharomyces species use in pregnancy . Probiotics are unlikely to be transferred into breast milk Probiotics have been proposed for a number of urogenital infectious conditions . In this study , we examine a possible effect on human papillomavirus (HPV)-related precancerous lesions in cervical cytology . We conducted a prospect i ve controlled pilot study , in which 54 women with an HPV+low- grade squamous intraepithelial lesion diagnosis in their PAP smear were followed for 6 months . The intervention group consumed a daily probiotic drink during the study period ; the control group received no treatment , according to common care policy . Outcome measures were the control PAP smear and HPV status after 6 months . Probiotic users had a twice as high chance of clearance of cytological abnormalities ( 60 vs. 31 % , P=0.05 ) . HPV was cleared in 19 % of control patients versus 29 % of probiotic users ( P=0.41 ) . This exploratory pilot study suggests that the probiotic studied promotes the clearance of HPV-related cytological abnormalities . If confirmed , this would represent an entirely new option to manage cervical cancer precursors This r and omized double-blind placebo controlled study assessed the vaginal colonization of lactic acid bacteria and clinical outcome . Vaginal capsules containing L gasseri LN40 , Lactobacillus fermentum LN99 , L. casei subsp . rhamnosus LN113 and P. acidilactici LN23 , or placebos were administered for five days to 95 women after conventional treatment of bacterial vaginosis and /or vulvovaginal c and idiasis . Vulvovaginal examinations and vaginal samplings were performed before and after administration , after the first and second menstruation , and after six months . Presence of LN strains was assessed using RAPD analysis . LN strains were present 2 - 3 days after administration in 89 % of the women receiving LN strains ( placebo : 0 % , p < 0.0001 ) . After one menstruation 53 % were colonized by at least one LN strain . Nine percent were still colonized six months after administration . Ninety-three percent of the women receiving LN strains were cured 2 - 3 days after administration ( placebo : 83 % ) , and 78 % after one menstruation ( placebo : 71 % ) ( ns ) . The intervention group experienced less malodorous discharge 2 - 3 days after administration ( p = 0.03 ) and after the second menstruation ( p = 0.04 ) , compared with placebo . In summary , five days of vaginal administration of LN strains after conventional treatment of bacterial vaginosis and /or vulvovaginal c and idiasis lead to vaginal colonization , somewhat fewer recurrences and less malodorous discharge
target: Probiotic interventions were effective for treatment and prevention of BV , prevention of recurrences of c and idiasis and UTIs , and clearing HPV lesions .
  Although clinical practice recommendations were limited by the strength of evidence , probiotic interventions were effective in treatment and prevention of urogenital infections as alternatives or co-treatments .
background: INTRODUCTION Probiotics are a complementary and integrative therapy useful in the treatment and prevention of urogenital infections in women .
  This study extends the work of research ers who systematic ally investigated the scientific literature on probiotics to prevent or treat urogenital infections .