Bacterial Vaginosis Recurrence Rates Research Articles

Unravelling the vaginal microbiome, impact on health and disease.

The vaginal microbiome has a fundamental role in supporting optimal vaginal, reproductive, and sexual health. Conversely, dysbiosis of the vaginal microbiome is linked to vaginal symptoms and adverse health outcomes. This review summarizes recent literature concerning the role of the vaginal microbiome in health and disease, with a focus on the most common vaginal dysbiosis, bacterial vaginosis. Molecular studies have expanded our understanding of the composition of the vaginal microbiome. Lactic acid-producing lactobacilli are an important component of host defences against pathogens, whereas a paucity of lactobacilli is associated with adverse sequelae. Bacterial vaginosis is characterized by low levels of lactobacilli and increased levels of nonoptimal anaerobes; however, the exact cause remains unclear. Furthermore, despite decades of research, bacterial vaginosis recurrence rates following standard treatment are unacceptably high. Strategies to improve bacterial vaginosis cure and promote an optimal lactobacilli-dominated vaginal microbiome are being investigated. Importantly, historical and emerging evidence supports the sexual transmission of bacterial vaginosis, which opens exciting opportunities for novel treatments that incorporate partners. A mechanistic and deeper understanding of the vaginal microbiome in health and disease is needed to inform ongoing development of therapeutics to improve bacterial vaginosis cure. Partner treatment holds promise for improving bacterial vaginosis cure.

Performance and Safety of a New Medical Device (Polybactum) for Reducing the Recurrence Rate of Bacterial Vaginosis: Protocol for a Multicenter, Open-Label, Noncontrolled International Clinical Trial (POLARIS Study).

The medical literature has reported that recurrent bacterial vaginosis (RBV) has a relapse rate of 35% within 3 months and 60% within 12 months after antibiotic administration. Products that are able to provide a barrier effect against the biofilm produced by Gardnerella vaginalis could play a role in improving the results of bacterial vaginosis (BV) treatment. This study aims to assess the performance and safety of a medical device (Polybactum) containing polycarbophil, lauryl glucoside, and glycerides (PLGG) for reducing the rate of recurrence of BV. The study includes women who are aged above 18 years, are willing to provide signed informed consent, have a diagnosis of BV according to the Amsel criteria, and have been affected by at least 2 episodes of RBV in the last 12 months. The trial includes 2 phases. In the first phase (according to an open-label noncontrolled design), the treatment involving PLGG is administered for 3 cycles and is followed by a 1-month period of follow-up without treatment. In the second phase, a 9-month follow-up period is envisaged. Thus, for each patient, a 10-month follow-up period without treatment is planned. The study involves 5 centers (2 in Italy and 3 in Romania). We calculated a sample size of 44 pairs to achieve a power of 80% and a 1-sided significance of 5% for detecting a difference of 0.25 between marginal proportions, in comparison with the mean recurrence rate of BV reported in the medical literature. We estimated a potential dropout rate of 20%, and thus, we decided to enroll 55 patients (1-group chi-square test). The study received ethics approval in 2016 in Romania and 1 year later in Italy. Recruitment started in September 2016. An interim analysis was performed in 2019, and full study analysis results are expected in July 2023. The tested medical device involving PLGG could modify the mechanisms involved in the pathogenesis of BV and could improve microbiological parameters owing to the acidifying effect on vaginal pH. We believe that the findings of our study could be useful for other investigators who want to test different products against RBV using a standardized protocol and standardized procedures. ClinicalTrials.gov NCT02863536; https://clinicaltrials.gov/ct2/show/NCT02863536. RR1-10.2196/42787.

Efficacy and safety of Fufang Furong Effervescent Suppository for the treatment of mixed vaginitis: a randomized, multicenter, and non-inferiority study

ObjectiveThe aim of this study was to compare the clinical efficacy and safety of Fufang Furong Effervescent Suppository and clindamycin phosphate cream for the treatment of bacterial vaginosis (BV) combined with aerobic vaginitis (AV). MethodsThis was a randomized, multicentre, active-controlled, non-inferiority clinical trial, with two parallel groups. Women diagnosed with BV + AV were randomly assigned to one of two groups and received 12-days of vaginal administration of either Fufang Furong Effervescent Suppository or clindamycin phosphate cream. The follow-up occurred during the 3–5 days (15–17 days) and 28 ± 3 days (40 ± 3 days) after drug administration, with the main assessments including the cure rate, BV, AV effective rate, recurrence rate, Lactobacillary grade (LBG) changes and adverse effects. The non-inferiority threshold of the non-inferiority test was set at 12%. ResultsFrom among the 600 eligible participants, 559 were randomly allocated to either the Furong group (n = 285) or the Clindamycin group (n = 274). The cure rate, BV, AV effective rate and the LBG changes of Furong group were not inferior to Clindamycin group in 15–17 days. The recurrence rate of BV + AV was also non-inferior to Clindamycin group at 40±3 days. During the follow-up period, no significant difference in the incidence of side effects were found between the two groups. ConclusionThe treatment of BV + AV using Fufang Furong Effervescent Suppository was not inferior to that of clindamycin phosphate cream in terms of cure rate, LBG changes, recurrence rate and adverse effects.

In vitro interactions within a biofilm containing three species found in bacterial vaginosis (BV) support the higher antimicrobial tolerance associated with BV recurrence.

Bacterial vaginosis (BV), the most common cause of vaginal discharge, is characterized by the presence of a polymicrobial biofilm on the vaginal epithelium, formed primarily by Gardnerella spp., but also other anaerobic species. Interactions between bacteria in multi-species biofilms are likely to contribute to increased virulence and to enhanced antimicrobial tolerance observed in vivo. However, functional studies addressing this question are lacking. To gain insights into the role that interactions between BV-associated species in multi-species BV biofilms might have on antimicrobial tolerance, single- and triple-species biofilms formed by Gardnerella vaginalis, Fannyhessea (Atopobium) vaginae and Peptostreptococcus anaerobius were characterized, before and after metronidazole or clindamycin treatment. Total biofilm biomass, total cells and cfu counts prior to and after antibiotic treatment were first determined. In addition, bacterial populations in the triple-species biofilms were also quantified by quantitative PCR (qPCR) and peptide nucleic acid (PNA) fluorescence in situ hybridization (FISH). Despite the effect observed in single-species biofilms, neither metronidazole nor clindamycin was effective in reducing triple-species biofilm biomass. Similar results were obtained when evaluating the number of total or culturable cells. Interestingly, despite differences between strain susceptibilities to antibiotics, the composition of the triple-species biofilms was not strongly affected by antibiotics. Taken together, these results strengthen the idea that, when co-incubated, bacteria can interact synergistically, leading to increased tolerance to antimicrobial therapy, which helps explain the observed clinically high BV recurrence rates.

The Role of Antimicrobial Resistance in Refractory and Recurrent Bacterial Vaginosis and Current Recommendations for Treatment.

Bacterial vaginosis (BV), the most common cause of vaginal discharge, is characterized by a shift in the vaginal microbiota from Lactobacillus species dominance to a diverse array of facultative and strict anaerobic bacteria which form a multi-species biofilm on vaginal epithelial cells. The rate of BV recurrence after therapy is high, often >60%. The BV biofilm itself likely contributes to recurrent and refractory disease after treatment by reducing antimicrobial penetration. However, antimicrobial resistance in BV-associated bacteria, including those both within the biofilm and the vaginal canal, may be the result of independent, unrelated bacterial properties. In the absence of new, more potent antimicrobial agents to eradicate drug-resistant pathogenic vaginal microbiota, treatment advances in refractory and recurrent BV have employed new strategies incorporating combination therapy. Such strategies include the use of combination antimicrobial regimens as well as alternative approaches such as probiotics and vaginal fluid transfer. Our current recommendations for the treatment of refractory and recurrent BV are provided.

A systematic review and meta-analysis on the efficacy of probiotics for bacterial vaginosis.

The current study aimed at assessing the overall efficacy of probiotics for the treatment of bacterial vaginosis (BV) through the review of relevant studies. A systematic literature review was conducted based largely on the following electronic databases updated to May 2021: Embase, the Cochrane Library, and PubMed, with the use of keywords. The investigators also thoroughly reviewed key pertinent sources in the literature for further inclusion. Eighteen studies including 1651 patients were selected in the present meta-analysis. In comparison with antibiotics, antibiotics plus probiotics significantly decreased the recurrence rate of BV (at 1-3 months and overall analysis) and increased the cure/remission rate of BV (at 1-3 months and overall analysis). Compared with placebo, probiotics decreased the recurrence rate of BV (at 1-3 months and overall analysis) and increased the cure/remission rate of BV (at 1-3 months). Compared with antibiotics, probiotics significantly decreased the recurrence rate of BV (at <1 month, 1-3 months and overall analysis) as well as the incidence of adverse events (AEs) (at less than 1 month) and increased the cure/remission rate of BV (at 1-3 months). In comparison with short-term probiotics treatment (<1 month), long-term probiotics treatment (1-3 months) yields superior beneficial outcomes and efficacy in the treatment of BV.

Эффективность коррекции цитокинового компонента локального иммунитета в лечении рецидивирующего бактериального вагиноза, ассоциированного с герпетической инфекцией

The risk of bacterial vaginosis (BV) and recurrence rate increase in the presence of herpesviruses, which is associated with changes in local immune response. Objective. To determine the effect of exogenous cytokines on the cytokine component in local immunity and its efficacy in the treatment of recurrent bacterial vaginosis (RBV) associated with herpesvirus infection. Patients and methods. Eighty women of reproductive age with RBV and herpesvirus infection were randomized into two groups: group I (n = 40) received Clindamycin and a complex of exogenous cytokines (Superlymph®), group II – Clindamycin and placebo. The biocenosis and cytokine levels in vaginal discharge were examined. Results. Recovery occurred in 95% (38/40) of patients in group I versus 77.5% (31/40) of those using placebo; p = 0.05, OR = 5.52 (95% CI: 1.11–27.43). The recurrence rate for 12 months was 12.6% (5/40) versus 33.5% (13/40), respectively, p = 0.01, with a 3-fold decrease in the risk of recurrence (OR = 0.30; 95% CI: 0.09–0.93). There was the restoration of vaginal biocenosis and the decrease in viral release and pro-inflammatory cytokine levels by an average of 1.5 times (p &lt; 0.001) compared with baseline values in patients who received Superlymph®. Conclusion. The complex of exogenous cytokines contributes to the normalization of cytokine component in local immune status and vaginal microbiota and to the decrease in recurrence rate of BV associated with herpesvirus infection. Key words: herpes infection, immunomodulatory therapy, recurrent bacterial vaginosis, Superlymph, cytokines

Treatment of Male Sexual Partners of Women With Bacterial Vaginosis: A Randomized, Double-Blind, Placebo-Controlled Trial.

We aimed to determine if treatment of male sexual partners of women with recurrent bacterial vaginosis (BV) with oral metronidazole 2×/day for 7 days (ie, multidose metronidazole) significantly decreased BV recurrence rates in the female. This was a multicenter, 2-arm, double-blind, placebo-controlled study. Women with recurrent BV and current diagnosis of BV by Amsel and Nugent were enrolled. Multidose metronidazole for 7 days was dispensed to women. Male partners were randomized to placebo versus multidose metronidazole for 7 days and asked to refrain from unprotected sex for 14 days. Female follow-up visits were conducted at day 21 and 8 and 16 weeks. Male follow-up visits occurred at days 14-21. BV cure was defined as 0-2 Amsel criteria and Nugent score 0-6 in the female partner with the primary endpoint at 16 weeks. 214 couples were enrolled. In the intent-to-treat population, there was no significant difference between treatment arms for the primary outcome. BV treatment failure occurred in 81% and 80% of women in the metronidazole and placebo arms through the third follow-up visit, respectively (P > .999). However, women whose male partners adhered to study medication were less likely to fail treatment (adjusted relative risk, .85; 95% CI, .73-.99; P = .035). This finding persisted in post hoc comparisons in the metronidazole arm. Overall, this study did not find that male partner treatment with multidose metronidazole significantly reduces BV recurrence in female partners, although women whose partners adhered to multidose metronidazole were less likely to fail treatment. (NCT02209519).

Evaluation of an Orally Administered Multistrain Probiotic Supplement in Reducing Recurrences Rate of Bacterial Vaginosis: A Clinical and Microbiological Study

Background: Bacterial vaginosis (BV) is the most common urogenital disease in women, affecting about 19% - 24% of them in reproductive ages annually and after treatment, a single recurrence or more may occur in up to 58% of women within 12 months. Objective: The aim was to evaluate the effectiveness of a new orally administered food supplement, containing different probiotic strains, on women of childbearing age after the antibiotic treatment when compared with no probiotic intake. Methods: A prospective study was undertaken on 62 patients with BV. All patients were cured with metronidazole vaginal formulations (5 g of 0.75% gel once daily for 5 days or 500 mg ovules once daily for 7 days), then after was offered the option of using a new an orally administered food supplement containing: Lactobacillus plantarum PBS067, Lactobacillus rhamnosus LRH020 and Bifidobacterium animalis lactis BL050, with a total viability of 3 × 109 CFU/capsule (Intimique® Femme). Among these women, 50 accepted to use the new orally food supplement, while 25 patients decided to use only metronidazole (control group). Results: The recurrence rate of BV after treatment with Intimique® Femme was about 16%, compared to 40% in the control group. The incidence of abnormal vaginal microbiota decreased in both groups, but it was significantly higher in the Intimique® Femme group at the end of treatment. Conclusion: This study showed that, in case of BV diagnosis, the complementary treatment of a strain-specific probiotic complex after antibiotics prophylaxis, is mandatory to reduce potential recurrences and cyclic use of further antibiotics.

Single dose metronidazole, tinidazole and ornidazole in the treatment of bacterial vaginosis - a comparative study

Background: Bacterial vaginosis (BV) is the most common cause of abnormal vaginal discharge. There is a lack of consensus on the etiologic agents or agents associated with BV, due to polymicrobial nature. There is high recurrence rate of BV and it is difficult to treat. Metronidazole is the drug of choice but newer nitroimidazoles are better alternatives with long half-lives and better tolerability. Methods: This was a prospective, comparative, randomized, single blinded study on 120 diagnosed cases of bacterial vaginosis, with symptomatic or asymptomatic abnormal vaginal discharge. Amsel’s criteria were used to diagnose bacterial vaginosis as well as to assess the response and classify the patients as cured, partially cured and not cured. Statistical analysis was done by Chi square test. The cure rate was compared considering metronidazole cure rate as gold standard. Results: At 1 week, the cure rate of tinidazole and ornidazole was 89.5% in both the groups, and at 4 weeks, it was 84.5% for both drugs (P <0.001). Metronidazole showed a cure rate of 65.7% at 4 weeks. Conclusions: Tinidazole and ornidazole have better cure rate as compared to metronidazole in cases of bacterial vaginosis.

Efficacy of Vitamin C Vaginal Tablets as Prophylaxis for Recurrent Bacterial Vaginosis: A Randomised, Double-Blind, Placebo-Controlled Clinical Trial

BackgroundThe aetiology of bacterial vaginosis (BV) is still unclear but it is currently considered to be a synergistic polymicrobial syndrome. BV can often arise as a chronic or recurrent disease. The reason for such recurrences is not well elucidated. Previous studies have suggested that vaginal vitamin C may be a useful treatment in reducing recurrence rate, by increasing vaginal acidification and thereby making up for the decrease in hydrogen peroxide that results from a reduction in the number of lactobacilli present. Based on the above-mentioned consideration, a study was performed that aimed to evaluate the effect of vitamin C in the prophylaxis of BV relapses.MethodsThis was a randomised, double-blind, placebo-controlled, parallel-group clinical trial. One hundred and forty-two women, after having been cured from a recent episode of BV by either metronidazole or clindamycin, were randomised to receive vitamin C (74 patients) or placebo (68 patients) as prophylaxis for six monthly cycles, starting within 24 hours of the determination of ‘BV cure’. The patients applied one vaginal tablet once a day for 6 consecutive days per month after menses.ResultsThe rate of BV recurrence during the first 3 months was considerably lower in the vitamin C group (6.8%) than in the placebo (14.7%) group. Considering a 6-month treatment period, the recurrence rate in the vitamin C group (16.2%) was significantly lower (P = 0.024) than in the placebo group (32.4%). Moreover, at the same time point, the survival analysis of Kaplan Meyer was significant in favour of the vitamin C group compared with the placebo group (P = 0.029).ConclusionsThe study showed that regular use of 250 mg ascorbic acid vaginal tablets on 6 days per month for 6 months after successful treatment of bacterial vaginosis halves the risk of recurrence from 32.4% to 16.2% (P = 0.024).

Efficacy of Oral Metronidazole with Vaginal Clindamycin or Vaginal Probiotic for Bacterial Vaginosis: Randomised Placebo-Controlled Double-Blind Trial

BackgroundTo determine if oral metronidazole (MTZ-400mg bid) with 2% vaginal clindamycin-cream (Clind) or a Lactobacillus acidophilus vaginal-probiotic containing oestriol (Prob) reduces 6-month bacterial vaginosis (BV) recurrence.MethodsDouble-blind placebo-controlled parallel-group single-site study with balanced randomization (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 randomly 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.Results450 18–50 year old females were randomized and 408 (91%), equally distributed between groups, provided ≥1 NS post-randomization and were included in analyses; 42 (9%) participants with no post-randomization 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.ConclusionCombining 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 RegistrationANZCTR.org.au ACTRN12607000350426

O3-S5.06 Double-blind randomised placebo controlled trial of oral metronidazole in combination with either vaginal clindamycin or an oestrogen-containing vaginal probiotic for the treatment of bacterial vaginosis

BackgroundTo determine if addition of vaginal clindamycin or an oestrogen-containing vaginal probiotic, to current recommended therapy for bacterial vaginosis (BV), oral metronidazole for 7 days, reduces 6 month recurrence rates.MethodsThree...

Treatment Considerations for Bacterial Vaginosis and the Risk of Recurrence

Recommended regimens for the treatment of bacterial vaginosis (BV) have similar efficacy; thus, the choice of treatment should consider additional factors such as risk of BV recurrence and side effect profile. The purpose of this study was to investigate BV recurrence rates and rates of acquiring vulvovaginal candidiasis (VVC) after different BV treatments in a commercially insured population. Private administrative insurance claims from 2004 to 2006 were used. Study subjects were continuously enrolled females 12-50 years of age who filled prescriptions for BV treatment (n=32,268). The four BV treatments (single-dose clindamycin vaginal cream (2%), multiple-dose clindamycin vaginal regimens, vaginal metronidazole, and oral metronidazole) were compared for rates of recurrent BV and VVC after treatment using multivariate analyses. Covariates included sociodemographic and clinical characteristics. Overall, the rate of BV recurrence (2.7%), and VVC posttreatment (2.9%) were low. Women who were treated with single-dose clindamycin vaginal cream (2%) showed no significant difference from women treated with oral metronidazole in the likelihood of BV recurrence. However, women who received other vaginal treatments were significantly more likely to experience BV recurrence compared with women who received oral metronidazole (p<0.01). Moreover, women who were treated with single-dose clindamycin vaginal cream (2%) and vaginal metronidazole were significantly less likely to have VVC compared with those treated with oral metronidazole (p<0.01). This study suggests that single-dose clindamycin vaginal cream (2%) may be a good alternative to oral metronidazole for the treatment of BV, given the low rates of recurrence and subsequent VVC demonstrated in this analysis.

Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis

Efficacy study of suppressive vaginal metronidazole in reducing recurrent symptomatic episodes of bacterial vaginosis. Multicenter prospective study with initial 10-day open-label metronidazole gel in which asymptomatic responders randomly assigned to receive twice weekly metronidazole vaginal gel or placebo for 16 weeks and off therapy for 12 weeks. Of 157 eligible women with recurrent bacterial vaginosis, 112 of 127 returning evaluable women (88.2%) responded clinically and were randomly assigned. During suppressive therapy, recurrent bacterial vaginosis occurred in 13 women (25.5%) receiving metronidazole and 26 (59.1%) receiving placebo (MITT analysis, relative risk [RR] 0.43, CI = 0.25-0.73, P = .001). During the entire 28-week follow-up, recurrence occurred in 26 (51.0%) on treatment compared with 33 (75%) on placebo (RR 0.68, CI = 0.49-0.93, P = .02). Probability for remaining cured was 70% for metronidazole compared with 39% on placebo, which declined to 34% and 18%, respectively, by 28 weeks follow-up. Adverse effects were uncommon; however, secondary vaginal candidiasis occurred significantly more often in metronidazole-treated women (P = .02). Suppressive therapy with twice-weekly metronidazole gel achieves a significant reduction in the recurrence rate of bacterial vaginosis; however, secondary vaginal candidiasis is common.

Treatment of male partners and recurrence of bacterial vaginosis: a randomised trial.

OBJECTIVE: To test the efficacy of treatment with clindamycin of a partner on the recurrence rate of bacterial vaginosis in women within 3 months from diagnosis. SUBJECTS: Eligible for the...