Treatment Of Bacterial Vaginosis Research Articles

The use of a lactic acid gel in the treatment and prevention of bacterial vaginosis and urinary tract infections as a challenge to antibacterial therapy. A literature review

Bacterial vaginosis and urinary tract infections are common conditions that lead to a decrease in the quality of life and significant economic costs. The review provides up-to-date information on the role of lactic acid in the microbiota of the vagina and urinary tract, as well as on the use of a lactic acid gel in these conditions. Bacterial vaginosis is associated with an increased risk of urinary tract infections. Antibacterial therapy demonstrates statistically significant results in treating exacerbation, but not preventing further relapses, which is due to the possible high ability of bacteria to form biofilms. Lactic acid, unlike hydrogen peroxide, is involved in maintaining the vaginal microbiota and enhancing its protective function against sexually transmitted infections, and indirectly affects the urinary microbiota. This may allow the use of lactic acid for the treatment and prevention of relapses in both bacterial vaginosis and urinary tract infections.

Microbiota disorders in bacterial vaginosis and the possibility of personalized therapy of the disease with the use of probiotics (review)

The review presents data on the etiology and treatment of bacterial vaginosis. Bacterial vaginosis is caused by the replacement of a protective microbiota in a lower part of a female reproductive tract with the pathogenic one. This disease is widespread in a world, in some cases it is asymptomatic, but is accompanied by complications, which include chorioamnionitis, inflammatory diseases of the pelvic organs, cervicitis, premature birth. In some cases, the disease is characterized by a recurrent course that requires a personalized treatment.

Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis.

Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2 = 62%, and 0.59 (95% CI 0.42, 0.82), I2 = 0 before; and 0.95 (95% CI 0.81, 1.11), I2 = 59%, and 0.90 (95% CI: 0.72, 1.12), I2 = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.

Response to antibiotic treatment of bacterial vaginosis predicts the effectiveness of LACTIN-v (lactobacillus crispatus CTV-05) in the prevention of recurrent disease

Live biotherapeutic products (LBPs) containing vaginal Lactobacillus are promising adjuvant treatments to prevent recurrent bacterial vaginosis (BV) but may depend on the success of initial antibiotic treatment.

Treatment Success Following Standard Antibiotic Treatment for Bacterial Vaginosis Is Not Associated With Pretreatment Genital Immune or Microbial Parameters.

Bacterial vaginosis (BV) is a proinflammatory genital condition associated with adverse reproductive health outcomes, including increased HIV incidence. However, BV recurrence rates are high after standard antibiotic treatment. While the composition of the vaginal microbiota before BV treatment may be linked to BV recurrence, it is unclear whether the preceding genital immune milieu is predictive of treatment success. Here we assessed whether baseline vaginal soluble immune factors or the composition of the vaginal microbiota predicted treatment success 1 month after metronidazole treatment in 2 separate cohorts of women with BV, 1 in the United States and 1 in Kenya; samples within 48 hours of BV treatment were also available for the US cohort. Neither soluble immune factors nor the composition of the vaginal microbiota before BV treatment was associated with treatment response in either cohort. In the US cohort, although the absolute abundances of key vaginal bacterial taxa pretreatment were not associated with treatment response, participants with sustained BV clearance had a more pronounced reduction in the absolute abundance of Gardnerella vaginalis immediately after treatment. Pretreatment immune and microbial parameters were not predictive of BV treatment success in these clinical cohorts.

Exploring the Efficacy of ZB-06 Vaginal Biofilm as a Novel Treatment for Recurrent Bacterial Vaginosis.

The purpose of this research was to investigate the efficacy of ZB-06 vaginal biofilm as a novel treatment for recurrent bacterial vaginosis (BV). BV is a prevalent vaginal infection that primarily affects women of reproductive age and is linked to adverse health outcomes. Biofilm production allows bacteria to cling to the vaginal epithelium, making antibiotics harder to penetrate and treat the illness efficiently. ZB-06 is a vaginal biofilm inhibitor that may dissolve the biofilm generated by the bacteria causing BV, enhancing antibiotic therapy efficacy and lowering the risk of recurrence. The current literature on BV, biofilm formation, and the possible function of ZB-06 as a therapy option for recurrent BV is reviewed in this article. More research is needed to determine ZB-06's safety and efficacy.

Подход к лечению бактериального вагиноза с применением комплекса бактериофагов

Introduction. A variety of treatment regimens for bacterial vaginosis (BV) pose to the clinician the question of choosing appropriate therapy for this disease. Aim. Improving the results of combination treatment of reproductive-age women with bacterial vaginosis by topical application of polyvalent bacteriophages. Materials and methods. A prospective study involving 120 female patients from 18 to 45 years old with complaints of abnormal vaginal discharge, diagnosis of BV confirmed by the Amsel criteria was performed. The patients were divided into 4 groups of 30 people, depending on the treatment regimen for BV: group 1 – metronidazole (gel) intravaginally + preparation Phagogyn (gel), polyvalent bacteriophage (PVB) for topical application; group 2 – clindamycin (cream) intravaginally + Phagogyn for topical application; group 3 – chlorhexidine gluconate (vaginal tablets) + Phagogyn for topical application; group 4 – Elzhina (ornidazole 500 mg, neomycin 65 000 U, prednisolone 3 mg, econazole 100 mg) + Phagogyn for topical application. Results. 10–14 days after the treatment, the effectiveness of metronidazole for vaginal application in combination with Phagogyn according to the Amsel criteria was 60.00%, clindamycin intravaginally in combination with Phagogyn – 73.33%, chlorhexidine gluconate intravaginally with Phagogyn – 43.33%, Elzhina + Phagogyn – 96.67%. Conclusion. The combination of Elzhina with Phagogyn is feasible for use in clinical practice to achieve better results in the treatment of BV, since this combination turned out to be the most effective.

Фармакотерапия бактериального вагиноза: антибиотики vs антисептики

Antimicrobial resistance is one of the public health challenges faced by physicians and scientists all over the globe. According to the antimicrobial resistance prevention strategy adopted in Russia, it is necessary to take measures to ensure rational prescribing and use of antibiotics and, in certain situations, to replace them with medications from other pharmacological groups. In some cases, antiseptics can be a worthy alternative to antibiotics. Dequalinium chloride is an antimicrobial antiseptic agent with a broad bactericidal and fungicidal activity, which allows the treatment of mixed vaginal infections. During intravaginal administration there is no penetration of the drug into the systemic bloodstream, so it is safe for use in clinical practice at any gestational age. The findings support a comparable efficacy of dequalinium chloride and clindamycin against mixed biofilms that are commonly formed on the vaginal mucosa; numerous clinical studies have demonstrated their comparable clinical efficacy in the treatment of bacterial vaginosis. Dequalinium chloride has multiple modes of action against pathogens, which makes the development of resistance to this agent unlikely and thus reduces the risk of resistant strains dominating the microbiome. Wider application of topical antiseptics in the pharmacotherapy for vulvovaginal infections will optimize antibiotic potency, limiting the growth of antimicrobial resistance. Key words: antimicrobial resistance, bacterial vaginosis, antiseptics, dequalinium chloride, pharmacotherapy

Деквалиния хлорид в терапии вагинальных инфекций

The most common inflammatory and infectious diseases of the lower genital tract include bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), aerobic vaginitis, and mixed infections. Standard modern therapies show acceptable but short-term efficacy in most cases, and high recurrence rates and increased antimicrobial resistance remain an unresolved issue. Moreover, vaginal infections are associated with different adverse outcomes both in terms of higher incidence of infertility among couples and gestational complications, having a serious impact on patients’ quality of life. The determination of appropriate management tactics for these women, especially in mixed infections, is quite a challenge for clinicians. This metaanalysis evaluates the efficacy of topical therapy with antimicrobial antiseptics containing dequalinium chloride for various types of vaginal infections. Objective. To analyze the clinical and microbiological efficacy and safety of dequalinium chloride in the treatment of vaginal infections of different etiologies. Materials and methods. A review of selected scientific publications over the past 40 years on the use of dequalinium chloride in the treatment of vaginal infections with assessing the efficacy and safety of its topical use in women was conducted. A total of 4,783 patients (from 26 studies) were included. Results. Dequalinium chloride is an antimicrobial antiseptic agent with broad bactericidal and fungicidal activity and low systemic absorption after vaginal administration. At the same time, dequalinium chloride has similar clinical efficacy to clindamycin when used topically in the treatment of bacterial vaginosis, and its broad antimicrobial activity appears to be most suitable for the treatment of mixed vaginal infections. In addition, the development of microbial resistance to this drug is unlikely due to its pluripotent mechanism of action and local application. Conclusion. The analysis showed that the current formulation of dequalinium chloride (10 mg vaginal tablets) as 6-day therapy with its broad spectrum of antimicrobial activity and good tolerability offers a safe and effective option for empiric therapy of various vaginal infections in daily practice. Key words: vaginal infections, bacterial vaginosis, vulvovaginal candidiasis, anaerobic vaginitis, dequalinium chloride

Бактериальный вагиноз: сравнительная оценка терапевтической эффективности 5-нитроимидазолов

Aim: to perform a comparative analysis of clinical and microbiological efficacy and compliance to treatment with 5-nitroimidazole derivatives in patients with bacterial vaginosis (BV). Patients and Methods: this prospective open randomized study included 96 patients diagnosed with BV. The patients were divided into two groups: group 1 (n=48) received antimicrobials — oral secnidazole 2000 mg in a single dose (decontamination therapy) and vaginally administered L. casei rhamnosus Doderleini for 14 days to restore the vaginal flora (contamination therapy); group 2 (n=48) received oral metronidazole 500 mg twice daily for 7 days (decontamination therapy) and vaginally administered L. casei rhamnosus Doderleini for 14 days (contamination therapy). Clinical efficacy was evaluated one and six months after the end of therapy. The treatment efficacy criteria included the absence of specific patient's complaints, clinical and laboratory findings (pH; Nugent score), and PCR results. The compliance to treatment was assessed using clinical and psychological tests (the Morisky-Green Scale and the Modified Medication Compliance Scale). The assessment of safety profile was based on the analysis of adverse events (AE). Results: one month after the end of treatment all patients had a statistically significant (p<0.05) reduction in the prevalence of BV symptoms (unpleasant vaginal odor, pathological vaginal discharge, itching, dyspareunia, dysuria events) as compared to those at the baseline. At month 1 after the end of treatment, subgroup analysis did not demonstrate a significant difference. Six months after the end of treatment the proportion of the group 1 patients who had pathological vaginal discharge with specific odor increased to 16.7%, while in the group 2 patients it reduced to 8.3% (p<0.05). Microbiological assessment (PCR) of the combination therapy in two groups of patients with BV demonstrated a high antibacterial efficacy of 5-nitroimidazole derivatives during the first month of follow-up. The patients were considered fully compliant if they scored 4 on the Morisky — Green Scale and scored 30 on the Modified Medication Compliance Scale of V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology. The percentage of full compliance was 76.2±2.8% in the group 1 patients and 93.75±3.25% in the group 2 patients. Conclusion: a high comparative clinical and microbiological effectiveness of treatments with 5-nitroimidazole derivatives (metronidazole and secnidazole) with further vaginal colonization with lactobacilli was demonstrated in patients with bacterial vaginosis. Full medication compliance was higher in patients receiving secnidazole for BV treatment. KEYWORDS: bacterial vaginosis, vaginal microbiota, vaginal discharge, 5-nitroimidazole derivatives, metronidazole, secnidazole, compliance. FOR CITATION: Kutsenko I.G., Borovikov I.O., Kravtsova E.I. et al. Bacterial vaginosis: comparative effectiveness of treatments with 5-nitroimidazole derivatives. Russian Journal of Woman and Child Health. 2023;6(2):78–87 (in Russ.). DOI: 10.32364/2618-8430-2023- 6-2-78-87.

Optimizing the vaginal microbiome as a potential strategy to reduce heterosexual HIV transmission.

Bacterial vaginosis (BV) is a proinflammatory genital condition characterized by high vaginal bacterial diversity and a paucity of Lactobacillus species. BV has been linked to an elevated risk of HIV acquisition among HIV-negative women and of forward HIV transmission to male sex partners among women living with HIV (adjusted hazard ratios of 1.69 and 3.17, respectively), potentially by eliciting genital inflammation in women with BV and their male sex partners. BV is also highly prevalent among women in sub-Saharan Africa, suggesting that BV treatment may have potential as an HIV prevention strategy. BV is typically treated with antibiotics but recurrence rates are high, possibly because treatment does not directly promote Lactobacillus growth. More recently, BV treatment strategies incorporating live biotherapeutic lactobacilli have led to sustained optimization of the vaginal microbiome and a decrease in inflammatory biomarkers previously associated with HIV susceptibility. Future studies are urgently needed to evaluate BV treatment strategies that can optimize the vaginal microbiome in the long term through colonization with H2 O2 -producing vaginal lactobacilli and to assess whether vaginal microbiota optimization is able to reduce the risk of HIV transmission.

The effectiveness of complex therapy in the treatment of nonspecific vaginitis in women of reproductive age

Objective. One of the most common gynecological pathologies among women of reproductive age is non-specific vaginitis. Bacterial vaginosis and aerobic vaginitis cause many obstetric and gynecological complications, and disease recurrence remains high. The aim of the study is to assess the effectiveness of complex therapy in the treatment of non-specific vaginitis in women of reproductive age.
 Materials and Methods. 160 women (100%) were examined, which were divided into 2 clinical groups with subgroups: the main group - 94 (58.8 %) patients with nonspecific vaginitis, who received treatment according to developed clinical diagnostic algorithms and schemes. The comparison group included 66 (41.2 %) patients with nonspecific vaginitis, who received treatment according to known protocols. Research methods: general (collection of complaints and anamnesis, gynecological examination, assessment of microscopy of vaginal smears according to the Amsel, Nugent and Donders criteria), laboratory (determination levels of follicle-stimulating, luteinizing hormones, prolactin, estradiol, adrenaline, noradrenaline, cortisol, magnesium in the blood), statistical.
 Results. Treatment of non-specific vaginitis according to complex schemes in the main group showed a significant decrease in the average follicle-stimulating hormone indicators – by 2.7 times, luteinizing hormone – by 2.6 times, prolactin – by 1.3 times (р<0,05) compares to the indicators before treatment. The estradiol level in the main group probably increased 1.3 times (р<0,05). The magnesium level also increased by an average of 1.4 times (р<0,05). Complex therapy in the main group significantly reduced the adrenaline levels by an average of 1.6 times, noradrenaline by 2.4 times, and cortisol by 1.8 times compared to the values before treatment (р<0,05). The proposed complex schemes are likely to improve the clinical effectiveness of drug treatment of non-specific vaginitis in the near and distant periods, which is accompanied by faster disappearance of complaints and normalization of the local condition during the gynecological examination (p<0,05), restoration of the vaginal microflora (p<0,05), a decrease frequency of recurrence in the main group of patients (c2=4,32; p<0,05).
 Conclusions. It is appropriate to use complex treatment of bacterial vaginosis and aerobic vaginitis in women of reproductive age.

Biofilm and pathogenic factor analysis of Gardnerella vaginalis associated with bacterial vaginosis in Northeast China.

Gardnerella vaginalis is a major pathogen responsible for bacterial vaginosis (BV). However, the recurrence of infection and the antibiotic resistance of biofilms remain significant challenges for the treatment of BV. In this study, we aimed to analyze the pathogenic factors and drug sensitivity associated with the clinical treatment of BV in Northeast China. Subgroups were identified by clade-specific polymerase chain reaction (PCR). Biofilm formation was measured by crystal violet staining, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The inhibition and eradication of biofilm formation were measured by XTT and broth recovery-based methods. Of the 24 samples of G. vaginalis, 11 samples and American Type Culture Collection (ATCC) 14018 formed biofilms; the remainder did not. The positive rates of detection for the sialidase A and vly genes in the 24 G. vaginalis samples were 100% and 79.2%, respectively. Moreover, 21 samples (87.5%) showed resistance to metronidazole and 16 (66.7%) presented with sensitivity towards clindamycin. The biofilm MIC80 (BMIC80) of metronidazole for ATCC14018 was 16 μg/ml while that of clindamycin was 0.125 μg/ml. The minimum biofilm eradication concentration (MBEC) of metronidazole was > 256 μg/ml while that of clindamycin was > 2 μg/ml. Our results revealed that G. vaginalis is more resistant to metronidazole than clindamycin and neither metronidazole nor clindamycin are able to effectively eradicate vaginal biofilms. Thus, the role of antibiotics and biofilms in BV requires further investigation.

The DEVA trial: protocol for a randomised controlled trial of dequalinium chloride versus usual care antibiotics for the treatment of bacterial vaginosis

BackgroundBacterial vaginosis (BV) is the most common cause of vaginal discharge in women of reproductive age, and it is estimated that up to a third of women will experience it at some point in their lives. BV produces an offensive vaginal odour and it is associated with serious sequelae. The most frequently prescribed treatment for BV in the UK is 7-day oral metronidazole but recurrences are common following it. Dequalinium chloride (Fluomizin©) is an anti-infective, antiseptic agent administered as a vaginal tablet. Small studies have shown this to be an effective alternative to antibiotics as a BV treatment. This trial aims to investigate whether dequalinium is as effective as current antibiotic treatments for the treatment of BV 1 month after treatment start.MethodsDEVA is a multi-centre, randomised, open-label, parallel group, non-inferiority trial of dequalinium chloride versus usual care antibiotics for the treatment of BV. Recruitment will take place in 15 GUM clinics in the UK with Leeds Sexual Health also managing remote recruitment via the trial website. Women will be randomised 1:1 to receive dequalinium or usual care antibiotics. The primary outcome is to determine if the proportion of women reporting resolution of BV symptoms 4 weeks after treatment (without the need for additional treatment) is not worse in women treated with dequalinium chloride compared to usual care antibiotics. Questionnaire follow-up will take place 4 and 12 weeks after starting treatment, and remotely recruited patients will also provide a week 4 BV vaginal smear. The sample size is 904.DiscussionThis trial will provide high-quality evidence on the use of dequalinium chloride as a BV treatment, which could result in patients reducing the number of antibiotics they take.Trial registrationISRCTN ISRCTN91800263. Prospectively registered on 20 January 2020.

Bacterial Vaginosis in Postmenopausal Women.

Bacterial vaginosis (BV) is the most common vaginal infection worldwide, but most research has been conducted in premenopausal women. After menopause, endogenous estrogen production decreases, often leading to the genitourinary syndrome of menopause (GSM), characterized by vulvovaginal dryness and irritation. The estrogen-deficient postmenopausal state results in an elevated vaginal pH and depletion of vaginal lactobacilli. Use of traditional BV diagnostics (Amsel criteria, Nugent score) is difficult in post-menopausal women, especially those not on estrogen replacement therapy, as these methods were originally developed in premenopausal women. In this review, we discuss recent clinical data on BV in postmenopausal women, difficulties in diagnosis using traditional methods, the role of BV molecular diagnostics, and our current expert opinion for managing BV in this population. BV prevalence has been found to range between 2%-57% among postmenopausal women per Amsel and Nugent criteria. This is likely an over-estimate of the true prevalence due to limitations in these criteria which were only validated in pre-menopausal women. Despite increasing diagnostic options for BV in recent years, including highly sensitive and specific BV nucleic acid amplification tests (NAATs), the physiologic changes of menopause and limited inclusion of postmenopausal women in clinical studies, diagnosis is difficult in this population. Recent studies utilizing 16s rRNA gene sequencing suggest that the vaginal microbiota of premenopausal and postmenopausal women is quite different, even if BV is not present. Data also suggest that obese postmenopausal women have significantly lower rates of BV compared to non-obese postmenopausal women, although further research is needed in this area. Multiple treatment options exist for vaginal atrophy and BV in this population. Data are limited regarding optimal diagnostic approaches for BV in postmenopausal women; BV NAATs and 16s rRNA gene sequencing may have a role for diagnosing BV in symptomatic women although further studies are needed. Menopausal women with characteristic vaginal symptoms and an elevated vaginal pH should be initially treated for estrogen deficiency prior to considering a diagnosis of BV; subsequent treatment for BV should be driven by symptoms.

Development of 3D-printed vaginal devices containing metronidazole for alternative bacterial vaginosis treatment

Bacterial vaginosis (BV) is an abnormal condition caused by the change of microbiota in the vagina. One of the most common bacteria found in the case of BV is Gardnerella vaginalis, which is categorised as anaerobic facultative bacteria. Currently, the available treatment for BV is the use of antibiotics, such as metronidazole (MTZ), in topical and oral dosage forms. The limitation of the currently available treatment is that multiple administration is required and thus, the patient needs to apply the drug frequently to maintain the drug efficacy. To address these limitations, this research proposed prolonged delivery of MTZ in the form of intravaginal devices made from biodegradable and biocompatible polymers. Semi-solid extrusion (SSE) 3D printing was used to prepare the intravaginal devices. The ratio of high and low molecular weight poly(caprolactone) (PCL) was varied to evaluate the effect of polymer composition on the drug release. The versatility of SSE 3D printer was used to print the intravaginal devices into two different shapes (meshes and discs) and containing two different polymer layers made from PCL and a copolymer of methyl vinyl ether and maleic anhydride (Gantrez™-AN119), which provided mucoadhesive properties. Indeed, this layer made from Gantrez™-AN119 increased ca. 5 times the mucoadhesive properties of the final 3D-printed devices (from 0.52 to 2.57 N). Furthermore, MTZ was homogenously dispersed within the polymer matrix as evidenced by scanning electron microscopy analysis. Additionally, in vitro drug release, and antibacterial activity of the MTZ-loaded intravaginal devices were evaluated. Disc formulations were able to sustain the release of MTZ for 72 h for formulations containing 70/30 and 60/40 ratio of high molecular weight/low molecular weight PCL. On the other hand, the discs containing a 50/50 ratio of high molecular weight/low molecular weight PCL showed up to 9 days of release. However, no significant differences in the MTZ release from the MTZ-loaded meshes (60/40 and 50/50 ratio of high molecular weight/low molecular weight PCL) were found after 24 h. The results showed that the different ratios of high and low molecular weight PCL did not significantly affect the MTZ release. However, the shape of the devices did influence the release of MTZ, showing that larger surface area of the meshes provided a faster MTZ release. Moreover, MTZ loaded 3D-printed discs (5% w/w) were capable of inhibiting the growth of Gardnerella vaginalis. These materials showed clear antimicrobial properties, exhibiting a zone of inhibition of 19.0 ± 1.3 mm. Based on these findings, the manufactured represent a valuable alternative approach to the current available treatment, as they were able to provide sustained release of MTZ, reducing the frequency of administration and thus improving patient compliance.

Antimicrobial Substances and Mechanisms of Lactobacillus rhamnosus against Gardnerella vaginalis.

Bacterial vaginosis (BV) is a common vaginal disease associated with abnormal changes in the vaginal microbiome. Our previous study found that Lactobacillus rhamnosus has a good therapeutic effect on bacterial vaginosis by inhibiting the most prominent bacterium associated with BV, Gardnerella vaginalis. In this study, we show that acetic acid and lactic acid are the main substances in the cell-free supernatant (CFS) of L. rhamnosus that inhibit the growth of G. vaginalis. Further study on the mechanism showed that acetic acid and lactic acid alter the morphology of the G. vaginalis cells, eventually causing the cells to shrink or burst, resulting in exudation of their intracellular contents. In addition, these two organic acids also dissipate the membrane potential of bacterial cells, affecting their synthesis of ATP. A reduced activity of the Na+/K+-ATPase leads to abnormal ATP metabolism, and ultimately inhibits the growth and reproduction of G. vaginalis. Our study provides valuable information for the widespread application of L. rhamnosus in the treatment of bacterial vaginosis.

Microbiological Assessment of Glycyrrhizic Acid Effectiveness in Bacterial Vaginosis – A Comparative Study

Background. Bacterial vaginosis (BV) is one of the most common female diseases, which is currently characterized by an increasing rate of clinical sign reccurence, the appearance of asymptomatic carriers, and atypical forms.
 This study was aimed to evaluate the effectiveness of glycyrrhizic acid administration in the prevention of BV recurrence.
 Materials and Methods. The study involved 88 women after BV treatment (metronidazole per os for seven days). Participants were randomly divided into two groups: the main group included 46 patients who were administered 0.1% glycyrrhizic acid intravaginally for three months after the main treatment; the control group comprised 42 women who received no anti-recurrence BV course. The effectiveness was assessed three and six months after the beginning of treatment and included gynecological examination and laboratory assessments (pH, amine test, microbiological investigation).
 Results. After recommended BV treatment without anti-recurrence course, the recurrence of laboratory criteria for BV increased three months after the treatment, including the increase in vaginal pH to > 4.5 in all subjects, positive amine test in 35.7% of patients, the presence of Gardnerella vaginalis at a concentration of 104-105 CFU/ml in 31.0% of women, reduction in the frequency of Lactobacillus detection with worsening of the condition and the onset of clinical manifestations of the disease six months later. In the main group, after glycyrrhizic acid administration, laboratory criteria of BV recovery three months after the treatment, and clinical and laboratory markers of BV recovery six months after the treatment were lower as compared to the control group.
 Conclusions. The anti-recurrence course of BV (vaginal administration of 0.1% glycyrrhizic acid) demonstrated a decrease in the frequency of complaints, clinical and laboratory markers, stabilization of the species composition of Lactobacillus, and a decrease in facultative anaerobe concentration in the vaginal microbiome as compared to group without anti-recurrence treatment.

Vaginal Lactobacillus iners abundance is associated with outcome in antibiotic treatment of bacterial vaginosis and capable of inhibiting Gardnerella.

Bacterial vaginosis is characterized as a polymicrobial dysbiosis with the loss of Lactobacillus spp. and growth of multiple anerobic bacteria, including Gardnerella, Prevotella and Atopobium ranked as the top three most abundant. A total of nine Gardnerella genomospecies have been identified, yet the association between their distribution or any exact Lactobacillus species with BV occurrence or prognosis remains controversial. A total of 308 patients and 62 healthy women who sought annual examinations were recruited, with 130 BV patients and 41 healthy women who met our inclusion criteria finally included. Vaginal samples were used for microscopic examination, 16S rRNA sequencing, bacterial culture and isolation. Isolates of Gardnerella vaginalis, Fannyhessae vaginae (used to be called Atopobium vaginae) and Lactobacillus iners were used for competition tests. We found that the relative abundances of Gardnerella, Prevotella and Atopobium were elevated in BV patients compared to healthy people (p<0.0001), yet no significant differences were found among patients with different clinical outcomes (p>0.05). Seven out of nine Gardnerella genomospecies were present in both BV patients and healthy women, and the relative abundances of all detected genomospecies were higher in BV patients (p<0.05). Cured patients possessed higher GS03 than intermediate and failed patients (p=0.005, 0.0337). L. iners was significantly higher in cured patients than in the other two groups (p=0.0021, p<0.0001), and its ability to inhibit the growth of G. vaginalis and F. vaginae was validated. In summary, seven Gardnerella genomospecies were detected in Chinese BV patients, but no association of its distribution and BV occurrence or prognosis was found. The relative abundance of L. iners was higher in cured patients, and its antimicrobial activity against G. vaginalis and F. vaginae was validated through in vitro inhibition experiment. L. iners could become a predictive indicator of clinical outcomes of BV patients, and its antimicrobial function might be beneficial to BV patients.

Vaginal formulations containing prebiotics and probiotics for treatment of bacterial vaginosis

Bacterial vaginosis (BV) is a common dysbiosis of the human vagina in which commensal vaginal lactobacilli are displaced by mixed pathogenic bacterial populations. Current treatments by antibiotics result in short- term cure but often lead to recurrence. Lactobacilli are being actively developed as a probiotic treatment option for BV, given their ability to inhibit growth of pathogenic microorganisms and to maintain the health and stability of the vaginal tract microbiota. Therefore, incorporation of freeze-dried lactobacillus and metronidazole (MET) into matrix-type silicone elastomer vaginal rings (VR) is a long-effective novel treatment of BV which can&amp;nbsp;also prevent recurrence. Here, MED-4870 matrix-type VRs containing four different lyoprotectants of three concentrations were manufactured by reaction injection molding, and Shore M Hardness test, compression test and twist test were applied to determine the impact of incorporation of lyoprotectants on mechanical characteristics of VRs. Results indicated that incorporation of lyoprotectants can increase the resistance force and decrease the rotational angles of the VRs. As the category and concentration of incorporated lyoprotectant also have impact on the releasing profile of MET and protecting ability of lactobacillus during freeze-drying process, more research such as&amp;nbsp;in-vitro&amp;nbsp;release tests and microbiology tests will be needed.