[Systematic review and Meta-analysis of efficacy and safety of Kushen Gelatum combined with antibiotics in treatment of bacterial vaginosis].

This study aims to systematically evaluate the clinical efficacy and safety of Kushen Gelatum combined with antibiotics for treating bacterial vaginosis. The randomized controlled trial(RCT) of Kushen Gelatum for treating bacterial vaginosis were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Cochrane Library with the time interval from inception to January 2023. Data were extracted from the included RCT by 2 investigators, including the sample size, characteristics of patients, interventions and controls, outcome indicators, and adverse effects. The Cochrane collaboration network's bias risk assessment tool was used for methodolo-gical quality evaluation of the included trials. RevMan 5.4 was employed to perform the Meta-analysis. A total of 19 RCTs were inclu-ded, involving 1 980 patients with bacterial vaginosis. Meta-analysis showed that, compared with nitroimidazoles alone, Kushen Gelatum + nitroimidazoles improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.24, 95%CI[1.13, 1.36], P<0.000 01), laboratory tests(RR=1.16, 95%CI[1.06, 1.26], P=0.000 9), and clinical symptoms(RR=1.26, 95%CI[1.08, 1.46], P=0.003), and reduced the leukocyte esterase positive rate(RR=0.29, 95%CI[0.17, 0.48], P<0.000 01) and the recurrence rate(RR=0.37, 95%CI[0.23, 0.58], P<0.000 1). Compared with lincomycin antibiotics(clindamycin) alone, Kushen Gelatum + lincomycin antibiotics(clindamycin) improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.06, 1.31], P=0.003) and laboratory tests(RR=1.27, 95%CI[1.04, 1.54], P=0.02), reduced the recurrence rate(RR=0.20, 95%CI[0.05, 0.75], P=0.02), and shortened the time to relief of burning sensation(MD=-1.70, 95%CI[-2.15,-1.26], P<0.000 01), vaginal itching(MD=-0.82, 95%CI[-1.30,-0.34], P=0.000 8), and abnormal leucorrhea(MD=-1.52, 95%CI[-1.98,-1.06], P<0.000 01). Compared with nitroimidazoles + probiotics, Kushen Gelatum + nitroimidazoles + probiotics improved the total response rate in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.02, 1.36], P=0.03) and reduced the recurrence rate(RR=0.27, 95%CI[0.09, 0.76], P=0.01). Kushen Gelatum combined with antibiotics demonstrates a potential therapeutic effect on bacterial vaginosis, whereas the number and quality of the relevant clinical studies remain to be improved. The process of clinical trial should be standardized to improve the quality of evidence, so as to provide strong evidence to guide the application of Kushen Gelatum in clinical practice.

Negative associations between folate and bacterial vaginosis in the NHANES 2001 to 2004.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common infections among women of reproductive age and accounts for 15-50% of infections globally. The role played by folate in the pathogenesis and progression of BV is poorly understood. The aim of this study was to investigate the association between serum folate, red blood cell (RBC) folate, and BV in American women. METHODS: 1,954 participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) program were included in this study. Multiple logistic regression was used to analyze the association between serum folate, RBC folate, and BV, and covariates including race, age, education level, and body mass index were used to construct adjusted models. Stratified analysis was used to explore the stability of the above associations in different populations. RESULTS: In the present cross-sectional study, we found that serum folate and RBC folate were inversely associated with the risk of BV. In the fully adjusted model, the risk of BV was reduced by 35% (OR=0.65, 95% CI: 0.51~0.83, p=0.0007) in the highest serum folate group and 32% (OR=0.68, 95% CI: 0.53~0.87, p=0.0023) in the highest RBC folate group compared to the lowest group. CONCLUSIONS: The results of this study indicated that serum folate and RBC folate were inversely associated with the risk of BV folate supplementation may play an important role in the prevention and management of BV.

Antimicrobial Effects of Sophora flavescens Alkaloids on Metronidazole-Resistant Gardnerella vaginalis in Planktonic and Biofilm Conditions.

Bacterial vaginosis (BV) is a common infectious disease of the lower female reproductive tract, which is characterized by the augmentation of anaerobic bacteria. Gardnerella (G.) vaginalis plays a predominant role in BV recurrence relating to its higher virulence potential and biofilm formation ability. With the increased proportion of metronidazole-resistant G. vaginalis, controlling resistance to metronidazole and finding more effective drugs became a major concern. In this study, 30 clinical strains were cultured from the vaginal secretions of BV patients, followed by PCR and 16S rDNA sequencing identification. According to the CLSI guidelines for anaerobic drug sensitivity testing, 19 strains were identified as metronidazole-resistant (minimum inhibitory concentration, MIC ≥ 32 µg/mL), of which 4 clinical strains were observed to be strong biofilm producer and the final minimum biofilm inhibitory concentration (MBIC) of metronidazole was increased to 512 µg/mL. Sophora flavescens Alkaloids (SFAs), a traditional chinese medicine, could not only inhibit the growth of metronidazole-resistant G. vaginalis in planktonic (MIC: 0.3125-1.25 mg/mL), but also eliminate the biofilm formation (MBIC: 0.625-1.25 mg/mL). In the high-magnification scanning electron, it was observed that the morphology of biofilm changed from a thick to flaky shape and was nearly depleted. These results indicate that SFAs could not only inhibit the growth of metronidazole-resistant G. vaginalisin planktonic and biofilm levels, but also destroyed the biofilm morphology and microstructure, which may contribute to the prevention of BV recurrence.

Impact of (recurrent) bacterial vaginosis on quality of life and the need for accessible alternative treatments.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common vaginal dysbiosis in women aged 15-44 years old. METHODS: We administered a cross-sectional, single timepoint survey to women ages 18 years or older and who have had bacterial vaginosis (BV). Women completed an anonymous online survey evaluating the impact of BV on their quality of life, how effective different types of treatments were and the amount of self-diagnosed vs. provider diagnosed BV episodes they had. RESULTS: 62 participants completed the anonymous online survey. With a self-reported median number of BV episodes in the past year was 4 (IQR 1-7). Among these women 69.8% reported BV had a negative impact on their sexual health, 67.7% on their physical health, 74.6% on their mental health. More than half of the respondents had used probiotics with oral Lactobacillus sp. (53.2%), mainly by oral route, and over a third had used vaginal boric acid (37.1%). Most women were unaware of Lactobacillus crispatus. Lactobacillus probiotics were more likely to be tried by women who were negatively impacted by BV for overall quality of life (p = 0.033), sexual health (p = 0.002), and mental health (p = 0.006) while boric acid use was more likely to be used by women who were negatively impacted by BV for their sexual health (p = 0.008). CONCLUSIONS: BV is associated with negative quality of life and the women most impacted are seeking alternative treatments such as probiotics (Lactobacillus) and boric acid. There needs to be improvements in BV treatment that include alternative therapy options that have demonstrated efficacy with standardized composition, formulation and dosage.

Effect of a combination of pea protein, grape seed extract and lactic acid in an in vivo model of bacterial vaginosis.

Bacterial vaginosis (BV) is a common vaginal dysbiosis characterized by a malodorous discharge and irritation. The imbalance of the vaginal microbiota plays a key role in the development of BV. It has been demonstrated that Gardnerella vaginalis (GV), a facultative anaerobic bacillus, is involved in BV. Due to the rising number of antimicrobial-resistant species, recurrence of BV is becoming more frequent in women; thus, alternative treatments to antibiotics are needed. Natural substances have recently shown a great efficacy for the treatment of vaginal dysbiosis. Thus, this study aimed to investigate the beneficial effect of a product containing pea protein (PP), grape seed extract (GS) and lactic acid (LA) in an in vivo model of Gardnerella vaginalis-induced vaginosis by intravaginal administration of GV suspension (1 × 106 CFU/20 µL saline). Our results demonstrated that the product containing PP, GS and LA significantly reduced GV proliferation. More specifically, it significantly preserved tissue architecture and reduced neutrophil infiltration, inflammatory markers and sialidase activity when used both as a pre- or a post-treatment. Moreover, the product displayed strong bioadhesive properties. Therefore, our data suggested that the product containing PP, GS and LA could be used as alternative preventive or curative treatment for the management of BV.

Efficacy and Safety of MED-01 Probiotics on Vaginal Health: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Bacterial vaginosis (BV) is the most common disease in women of childbearing age and is caused by the growth of abnormal microbiota in the vagina. Probiotic consumption can be an effective alternative treatment to preserve or improve vaginal health. In the present study, MED-01, a complex of five strains of probiotic candidates isolated from the vagina of Korean women, was used. This study was designed as a 12-week, randomized, multicenter, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of MED-01 on vaginal health. A total of 101 reproductive-aged women with a Nugent score of 4-6 took MED-01 (5.0 × 109 CFU) or a placebo once a day, and 76 participants completed the procedure. MED-01 significantly reduced the Nugent score compared with the placebo. Quantitative PCR analysis confirmed that Lactobacillus plantarum was significantly increased in the vagina, whereas harmful bacteria such as Mobiluncus spp., Gardnerella vaginalis, and Atopobium vaginae were suppressed after 12 weeks of MED-01 ingestion. No adverse events to the test food supplements were observed in the participants. These results confirmed that MED-01 can be used as a probiotic for treating BV, as it improves the vaginal microbiota.

Vaginal colonization of women after oral administration of Lactobacillus crispatus strain NTCVAG04 from the human microbiota.

BACKGROUND: The genomic approach has deeply changed the microbiology perspective, mainly concerning the microbioma identification. In this regard, some microbes colonize the healthy vagina. Vaginitis is a common gynecological ailment and includes bacterial vaginosis (BV), usually caused by local dysbiosis, such as a microbiota imbalance. Lactobacilli are the most prevalent bacteria colonizing the healthy vagina, so guaranteeing local eubiosis. In particular, vaginal colonization by L. crispatus is associated with low susceptibility to BV. Therefore, probiotics, such as life bacteria providing health advantages, are a current strategy in the prevention or treatment of vaginitis, including BV. However, there is a low level of evidence that probiotics after ingestion could really colonize the vagina. In particular, no study evidenced that L. crispatus after ingestion can colonize vagina. Therefore, the current study explored the capacity of Biovaginil® (NTC, Milan, Italy) dietary supplement containing Lactobacillus crispatus NTCVAG04 and vitamin A to colonize the gut and vagina in women with a history of vaginitis/vaginosis. METHODS: Twenty fertile females (mean age 34.0 years) were enrolled in the study. Rectal and vaginal swabs were collected at baseline and after the first and second cycle of Biovaginil®. Each cycle lasted 14 days within two consecutive menstrual periods. RESULTS: Seven women were excluded from the analysis because the samples were technically not evaluable. One woman dropped out because of mild adverse event. At the end of the study, nine women (75%) had positive rectal swab for L. crispatus NTCVAG04, and 8 of them also had positive vaginal swab. CONCLUSIONS: The current study provided the first evidence that L. crispatus NTCVAG04, administered by two Biovaginil® courses, colonized both the gut and vagina. Moreover, the L. crispatus NTCVAG04 strain could be considered the archetype of a new class of oral probiotics that actively colonize the vagina, and that could be called "colpobiotics."

Actividad antimicrobiana in vitro del extracto de hojas de Bixa orellana L. contra bacterias anaerobias asociadas a la vaginosis bacteriana y Lactobacillus spp / In vitro antimicrobial activity of Bixa orellana L. leaves extract against anaerobic bacteria associated to bacterial vaginosis and Lactobacillus spp.

Objetivos . Describir la actividad antimicrobiana in vitro del extracto metanólico de las hojas de Bixa orellana L. contra las bacterias anaerobias asociadas a la vaginosis bacteriana y Lactobacillus spp. Materiales y métodos . Se incluyeron en el estudio ocho cepas de referencia ATCC; Gardnerella vaginalis, Prevotella bivia, Peptococcus niger, Peptostreptococcus anaerobius, Mobiluncus curtisii, Atopobium vaginae, Veillonella parvula y Lactobacillus crispatus, y 22 aislamientos clínicos; once aislados de Gardnerella vaginalis y once aislados de Lactobacillus. La susceptibilidad antimicrobiana se determinó mediante el método de difusión en agar. La concentración mínima inhibitoria (CMI) y la concentración bactericida mínima (CBM) fueron determinadas utilizando el método de dilución en agar y un método de dilución modificado, respectivamente. Resultados . Todas las cepas de referencia ATCC tuvieron un alto nivel de susceptibilidad al extracto, con excepción de P. vibia, V. parvula y L. crispatus. Interesantemente, los aislamientos clínicos de G. vaginalis y la cepa ATCC de G. vaginalis fueron los más susceptibles al extracto dados los bajos valores de CMI (1,0 - 2,0 mg/mL) y CBM (1,0 - 4,0 mg/mL), mientras que, los aislamientos clínicos de Lactobacillus spp. y la cepa ATCC de L. crispatus fueron los menos susceptibles debido a los altos valores de CMI (32,0 mg/mL) y CBM (≥ 32,0 mg/mL). Conclusiones . Los experimentos in vitro sugieren que el extracto posee propiedades antibacterianas selectivas dada su alta actividad contra bacterias anaerobias asociadas a vaginosis bacteriana y baja actividad contra especies de Lactobacillus.

Objective. To describe the in vitro antimicrobial activity of the methanolic extract of Bixa orellana L. leaves against anaerobic bacteria associated to bacterial vaginosis and Lactobacillus spp. Materials and methods. Eight ATCC reference strains; Gardnerella vaginalis, Prevotella bivia, Peptococcus niger, Peptostreptococcus anaerobius, Mobiluncus curtisii, Atopobium vaginae, Veillonella parvula, and Lactobacillus crispatus, and twenty-two clinical isolates; eleven Gardnerella vaginalis and eleven Lactobacillus strains, were included in the study. The antimicrobial susceptibility was determined by the agar diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by using agar dilution and a modified dilution plating method, respectively. Results. All ATCC reference strains showed high levels of susceptibility to the extract, except P. vibia, V. parvula and L. crispatus. Interestingly, all G. vaginalis clinical isolates and the G. vaginalis ATTC strain were the most susceptible to the extract, given their low MIC (1.0 - 2.0 mg/mL) and MBC (1.0 - 4.0 mg/mL) values, whereas, the Lactobacillus spp. clinical isolates and the L. crispatus ATCC strain were the least susceptible bacteria given their high MIC (32.0 mg/mL) and MBC (≥ 32.0 mg/mL) values. Conclusions. In vitro experiments suggest that the extract possesses selective antimicrobial properties given its high activity against bacterial vaginosis-associated anaerobic bacteria and low activity against Lactobacillus species.

Accurate 16S Absolute Quantification Sequencing Revealed Vaginal Microecological Composition and Dynamics During Mixed Vaginitis Treatment With Fufang FuRong Effervescent Suppository.

Background: The diagnosis and treatment of mixed vaginitis are more complicated than single pathogenic infections, and there may be adverse reactions and several contraindications to conventional antibiotic therapy. Therefore, this study aimed to evaluate the preliminary effects of Fufang Furong Effervescent Suppository for the management of aerobic vaginitis (AV) mixed with bacterial vaginosis (BV) using Accurate 16S absolute quantification sequencing (Accu16S). Methods: In the present randomized, blind, multi-center clinical trial, women (20 to 55 years) who had received a diagnosis of AV+BV were randomly assigned into clindamycin positive control (n = 41) and Fufang Furong Effervescent Suppository (n = 39) groups. The follow-up occurred in three time periods (V1: -2~0 days; V2: 15-17 days; V3: 40 ± 3 days). At each visit, two vaginal swabs, one for clinical evaluation and one for laboratory examination, were taken from each patient. The Nugent score, Donders' score, drug-related complications, recurrence rates, and microecological changes of vaginal swabs were assessed in the time three periods. Results: At baseline, the two groups were similar in frequency of presentation with vaginal burning, odor, abnormal discharge, and itching. No meaningful differences in Nugent and Donders' scores were detected between the two groups at stage V2 (Nugent: p = 0.67; Donders': p = 0.85) and V3 (Nugent: p = 0.97; Donders: p = 0.55). The Furong group presented fewer complications compared to the Clindamycin group. However, this difference was not statistically significant (p = 0.15). Additionally, Accu16S indicated that the total abundance of bacteria in both groups sharply decreased in stage V2, but slightly increased in V3. In stage V3, the absolute abundance of Lactobacillus in the Furong group was considerably higher compared to untreated samples (p < 0.05). On the other hand, no momentous increase was detected in the Clindamycin group (p > 0.05). Conclusion: Fufang Furong Effervescent Suppository can be as effective as clindamycin cream in the management of AV+BV while may restore the vagina microecosystem better.

Dequalinium chloride use in adult Spanish women with bacterial vaginosis: an observational study.

Bacterial vaginosis (BV) represents the most frequent vaginal infection in women of childbearing age. The aim of this study was to characterise episodes of BV among adult Spanish women and their management with dequalinium chloride (DQC). Data from 573 DQC-treated BV adult women was obtained on medical records and questionnaires. The study shows that 20.6% had presented vaginal infections previously. Comorbid candidosis was significantly associated to other symptoms, such as pruritus or leucorrhoea. Most patients (64.3%) indicated a moderate-strong impact of the BV episode on their sexual life. After treatment, 84.8% of patients reported no BV symptoms. Patients were given instructions to prevent relapses. Most patients (83.1%) rated DQC as 'satisfactory' or 'very/extremely satisfactory' regarding symptom relief, prevention or treatment of the episode of BV. In conclusion, this study provides a better understanding of BV episodes and the impact of the treatment with DQC in real clinical practice in Spanish patients.IMPACT STATEMENTWhat is already known on this subject? Bacterial vaginosis (BV) is the most commonly reported vaginal infection among women of childbearing age. Despite the availability of antibiotic medications for the treatment of BV, management of this condition remains challenging. In fact, recurrence of BV has been reported for up to 50% of cases. However, antiseptic agents are considered an effective option for BV treatment.What the results of this study add? The study provides a better understanding of the prevalent symptomatology and the impact on quality of life of women with BV. Moreover, it has been observed that antiseptic dequalinium chloride (DQC) efficiently reduces symptoms and improves quality of life of the patients during episodes of BV.What the implications are of these findings for clinical practice and/or further research? In the context of the World Health Organisation recommendations on the rational use of antibiotics, we believe that the use of DQC may be a good alternative to antibiotics as a therapy for BV.

Lactobacillus plantarum Lp62 exerts probiotic effects against Gardnerella vaginalis ATCC 49154 in bacterial vaginosis.

The severe side-effects elicited by conventional antibiotic therapy and the recurrence of Bacterial vaginosis-associated bacteria and bacterial resistance have led to the development of novel alternative therapies, among which genital probiotics are widely used. In this study, we aimed to evaluate the antimicrobial activities of Lactobacillus plantarum Lp62 and its supernatant against Gardnerella vaginalis, using both in vitro and in vivo approaches. In vitro assays were used to evaluate the viability of the strain and the antimicrobial activities of the supernatant in different pH ranges. An in vivo assay was performed on female BALB/c mice, wherein the animals were divided into eight groups: four control groups and four treated groups (for curative and preventive therapies). After infecting and treating the mice, the animals were killed to quantify the bacterial load using qPCR, evaluate leucocyte cellular response, determine vaginal cytokine levels and perform cytokine tissue gene expression. Our analyses revealed significant activity of the strain and its supernatant against G. vaginalis. Preliminary in vitro tests showed that the strain grew with equal efficiency in different pH ranges. Meanwhile, the presence of halo and inhibition of pathogen growth established the significant activity of the supernatant against G. vaginalis. We observed that both micro-organisms are resident bacteria of mouse microbiota and that the lactobacilli population growth was affected by G. vaginalis and vice versa. We also observed that the treated groups, with their low bacterial load, absence of leucocyte recruitment, reduced cytokine levels in the vaginal lavage and normalized cytokine gene expression, successfully controlled the infection.

The reproductive tract microbiota in pregnancy.

The reproductive tract microbiota plays a crucial role in maintenance of normal pregnancy and influences reproductive outcomes. Microbe-host interactions in pregnancy remain poorly understood and their role in shaping immune modulation is still being uncovered. In this review, we describe the composition of vaginal microbial communities in the reproductive tract and their association with reproductive outcomes. We also consider strategies for manipulating microbiota composition by using live biotherapeutics, selective eradication of pathogenic bacteria with antibiotics and vaginal microbiota transplantation. Finally, future developments in this field and the need for mechanistic studies to explore the functional significance of reproductive tract microbial communities are highlighted.

Effect of probiotics on vaginal Ureaplasma parvum in women suffering from unexplained infertility.

RESEARCH QUESTION: Does oral probiotic supplementation influence the relative abundance of different vaginal microbiota in women experiencing infertility? DESIGN: A prospective, monocentric randomized controlled trial. To study the influence of probiotics on infertility, 80 patients with primary or secondary infertility were included. Patients were assigned to either a probiotic treatment or a control group. Participants in the treatment group (n = 40) took one sachet (2 g) a day of a defined probiotic supplement limiting Lactobacillus strains. Patients in the control group did not receive any additional probiotic supplements. Vaginal samples were taken on day 20 of the menstrual cycle and 4 weeks later, on day 20, of the consecutive cycle. Subsequently, 16s rRNA gene analysis of the vaginal samples was conducted. RESULTS: After the intervention phase, no effects on alpha diversity resulting from treatment could be observed. The between sample diversity of different women (beta diversity) at baseline had no effects of age, treatment group or body mass index. Primary or secondary sterility, however, had a significant effect on community. Three clusters (Lactobacillus crispatus, Lactobacillus iners and Lactobacillus gasseri) were identified as the leading representatives. Furthermore, patients treated with probiotics showed limited growth of Ureaplasma parvum compared with the control group (P = 0.021). CONCLUSIONS: This study points to a possible protective effect of probiotic supplements on the vaginal microbiota. It is tempting to speculate that this effect assists in containing the growth of non-beneficial bacteria and helps to prevent or cure a dysbiotic vaginal flora.

Chlorhexidine, clotrimazole, metronidazole and combination therapy in the treatment of vaginal infections.

This was a clinical trial study that aimed to investigate the efficacy of vaginal chlorhexidine gel in the treatment of vulvovaginal candidiasis, bacterial vaginosis, and nonspecific vaginitis. The study population included patients who complained of vaginal discharge and presented to our University Gynecology Clinic. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) software. The student t-test and Mann-Whitney U test were used to analyze the quantitative and ordinal data, respectively. In order to analyze the qualitative data, the Chi-square or Fischer's exact tests were used. The mean satisfaction score in the vulvovaginal candidiasis patients who received chlorhexiine vaginal gel was 9.06 and 8.29 in the patients who received clotrimazole vaginal cream. The Mann-Whitney test did not show a statistically significant difference between mean scores of VAS in these two groups with vulvovaginal candidiasis (P=0.027). Among the patients with bacterial vaginosis, the mean satisfaction score was 8.91 in the chlorhexidine vaginal gel group and 8.72 in the metronidazole tablet group (P=0.607). In the nonspecific vaginitis group, the mean satisfaction score was 8.83 in the chlorhexidine vaginal gel group and 9.17 in the combination group (metronidazole + clotrimazole vaginal cream)(P=0.401). The highest mean visual analog scale score (VAS) score was documented in the combination therapy group. We found that chlorhexidine vaginal gel is a more effective method for the treatment and improvement of vaginal infections. The benefits of chlorhexidine gel have a positive therapeutic effect as a single drug in nonspecific vaginitis, rather than simultaneous administration of two agents.

Clinical research on traditional Chinese medicine treatment for bacterial vaginosis.

Bacterial vaginosis (BV) is a common disease among women of reproductive age, with a serious impact on their daily life and health. At present, the most common treatment for BV is to take antibiotics, which results in good short-term treatment effects, but poor long-term effects. Traditional Chinese medicine (TCM) has been used to treat BV for over a millennium, with little risk of triggering drug resistance and adverse effects. Based on syndrome differentiation, there are three oral TCM treatment strategies for BV, including invigorating spleen, clearing dampness and heat, and nourishing kidney. The oral TCM prescriptions, such as Yi Huang decoction, Longdan Xiegan decoction, Zhibai Dihaung decoction, and so on are commonly used. Topical TCM treatment is also popular in China. According to the research results of pharmacological effects of active TCM ingredients, the most potential mechanisms of TCM for BV treatment are immune-enhancement effects, antibacterial activity, and estrogen-liked effects. Nonetheless, the multi-constituent of herbs may result in possible disadvantages to BV treatment, and the pharmacological mechanisms of TCM need further study. Here, we provide an overview of TCM compounds and their preparations used for BV, based on the pathogenesis and the potential therapeutic mechanisms, therefore providing a reference for further studies.

Evaluación de la eficacia y seguridad del policresuleno en el tratamiento de la vaginitis mixta, Armenia, Colombia, 2017-2019. Estudio aleatorizado / Evaluation of the efficacy and safety of policresulen in the treatment of mixed vaginits, Armenia, Colombia, 2017-2019. Randomized study

Objetivo: evaluar la eficacia y seguridad de la adición de policresuleno a la terapia oral fluconazol ­ secnidazol, en mujeres con vaginitis mixta. Materiales y métodos:ensayo clínico aleatorizado, triple ciego, paralelo, controlado con placebo. Realizado en una clínica universitaria de Armenia (Colombia) entre 2017 y 2019. Participaron 122 mujeres mayores de 18 años, diagnosticadas de vaginitis mixta. El diagnóstico microbiológico se hizo mediante tinción de Gram, con posterior lectura del puntaje de Nugent y coloración de May Grunwald Giemsa prolongado, microscopía con KOH y frotis directo en fresco; se midió el pH con papel tornasol. Se les suministró terapia combinada de fluconazol-secnidazol oral más policresuleno vaginal (grupo «A¼, n=62) versus fluconazol-secnidazol oral más placebo vaginal (grupo «B¼, n=60). Se evaluó la mejoría de los síntomas, la tasa de curación y el porcentaje de satisfacción con la terapia. Resultados: la edad promedio fue de 29,75 ± 4,61 años. La mejoría de la sintomatología, al tercer día, fue mayor en el grupo «A¼ (85,48 % vs 68,33 %, p=0,001). Al final la tasa de curación (eficacia) fue superior en el grupo «A¼ (98,38 % vs 86,66 %) (p = 0,001). La satisfacción con el tratamiento administrado, alcanzó el 96,77 % (grupo «A¼) versus 93,33 % (grupo «B¼), (p = 0,411). El 27,41 % de las mujeres del grupo «A¼ y el 13,33 % del grupo «B¼ presentaron dos o más efectos secundarios (p = 0,001). Conclusiones: la combinación fluconazol - secnidazol oral más policresuleno vaginal, reporta una eficacia del 98,38 % para curar la vaginitis mixta, con satisfacción del 96,77 %..Au

Objective: to evaluate the efficacy and safety of the addition of policresulen to oral fluconazole - secnidazole therapy, in women with mixed vaginitis. Materials and methods:randomized, triple blind, parallel, placebo controlled clinical trial. In a university clinic in Armenia (Colombia); between 2017 and 2019. 122 women over 18 years of age,diagnosed with mixed vaginitis, participated. The microbiological diagnosis was made by Gram staining, with subsequent reading of the Nugent score and prolonged May Grunwald Giemsa staining, KOH microscopy and direct fresh smear; pH was measured with litmus paper. They were given combined fluconazole-oral secnidazole plus policresulen vaginal therapy (group "A", n = 62) versus oral fluconazole-secnidazole plus placebo vaginal (group "B", n = 60). Symptom improvement, cure rate and percentage of satisfaction with therapy were evaluated. Results: the improvement of the symptoms, on the third day, was greater in group «A¼ (85.48% vs 68.33%, p = 0.001). In the end, the cure was superior in group «A¼ (98.38% vs. 86.66%) (p = 0.001). Satisfaction with the administered treatment reached 96.77% (group "A") versus 93.33% (group "B"), (p = 0.411). 27.41% of the women in group «A¼ and 13.33% of group «B¼ presented two or more side effects (p = 0.001). Conclusions: the oral fluconazole -secnidazole plus vaginal polyresulene combination reports an efficacy of 98.38% to cure mixed vaginitis, with 96.77% satisfaction..Au

Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health.

Human vagina is colonised by a diverse array of microorganisms that make up the normal microbiota and mycobiota. Lactobacillus is the most frequently isolated microorganism from the healthy human vagina, this includes Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii. These vaginal lactobacilli have been touted to prevent invasion of pathogens by keeping their population in check. However, the disruption of vaginal ecosystem contributes to the overgrowth of pathogens which causes complicated vaginal infections such as bacterial vaginosis (BV), sexually transmitted infections (STIs), and vulvovaginal candidiasis (VVC). Predisposing factors such as menses, pregnancy, sexual practice, uncontrolled usage of antibiotics, and vaginal douching can alter the microbial community. Therefore, the composition of vaginal microbiota serves an important role in determining vagina health. Owing to their Generally Recognised as Safe (GRAS) status, lactobacilli have been widely utilised as one of the alternatives besides conventional antimicrobial treatment against vaginal pathogens for the prevention of chronic vaginitis and the restoration of vaginal ecosystem. In addition, the effectiveness of Lactobacillus as prophylaxis has also been well-founded in long-term administration. This review aimed to highlight the beneficial effects of lactobacilli derivatives (i.e. surface-active molecules) with anti-biofilm, antioxidant, pathogen-inhibition, and immunomodulation activities in developing remedies for vaginal infections. We also discuss the current challenges in the implementation of the use of lactobacilli derivatives in promotion of human health. In the current review, we intend to provide insights for the development of lactobacilli derivatives as a complementary or alternative medicine to conventional probiotic therapy in vaginal health.

The effect of Quercus (Oak Gal) vaginal cream versus metronidazole vaginal gel on bacterial vaginosis: A double­blind randomized controlled trial.

OBJECTIVE: This study was aimed to compare the effect of an Oak Gall extract­based cream and a metronidazole Gel on the bacterial vaginosis among women in reproductive age. MATERIAL AND METHODS: This was a double-blind, randomized controlled trial performed on 84 women with BV in reproductive age. Accordingly, the women were randomly assigned to the Oak Gall (n = 42) or metronidazole (n = 42) groups. Diagnosis of BV was confirmed when at least 3 of the 4 Amsel criteria were met by the participants (whitish-grey or thin homogeneous discharge, pH ≥ 4.5, the release of a fishy odor on the addition of 10 % KOH, and detection of clue cells > 20 % in the microscopic examination). For each group, either a methanol extract of Oak Gall vaginal cream or a metronidazole vaginal gel (5 g) was used as intravaginal for 5 consecutive days, and all the signs or symptoms were assessed by passing 4-7 days from the treatment completion. RESULTS: At baseline, the two groups were homogenous in terms of the vaginal burning, odor, dysuria, dyspareunia, and itching. Also, all women in both groups were free of symptoms (vaginal itching and burning sensation, bad odor, dysuria, and dyspareunia) by passing one week from the intervention (p < 0.001). The percent of bacterial vaginosis treatment was in 33(82.1 %) patients in terms of Oak Gall group and in 34(87.5 %) patients of Metronidazole group (p=0.56). Notably, Oak Gall was as effective and safe as metronidazole in the treatment of BV in reproductive-aged women. CONCLUSION: Oak Gall could be recommended for women in reproductive age who are uncomfortable with the potential side effects of synthetic drugs.

Bacterial vaginosis in pregnancy - a storm in the cup of tea.

Human vaginal microbiota is dominated by Lactobacillus spp both in the non-pregnant and pregnant state. Bacterial vaginosis (BV) is an imbalance of vaginal microbiota caused by a reduction in the normal lactobacillary bacteria, and a heavy over-growth of mixed anaerobic bacteria. Various clinical (Amsel's Criteria), laboratory (Nugent's score) and molecular diagnostic method (quantitative PCR) are used for diagnosis. BV in pregnancy is associated with increased risk of preterm birth, low birth weight, chorioamnionitis and postpartum endometritis, apart from bothersome vaginal discharge. Antibiotic treatment with metronidazole or clindamycin are effective in eradicating bacterial vaginosis and safe to use in pregnancy. Treatment of bacterial vaginosis has not been shown to improve obstetric outcomes in women at low risk of preterm birth, but may reduce the risk of preterm birth and low birth weight in women at increased risk of preterm birth. Routine screening and treatment is not recommended in low risk women. Test for cure should be performed after treatment. Further research is required on other treatment modalities such as probiotic therapy and microbiota transplantation.

Testing the regulatory framework in South Africa - a single-blind randomized pilot trial of commercial probiotic supplementation to standard therapy in women with bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) increases HIV risk and adverse reproductive outcomes. Standard-of-care (SOC) for BV are antibiotics; however, cure rates are low. Probiotics for vaginal health may be useful in improving cure and recurrence although the regulatory framework governing probiotics and the conduct of randomized clinical trials to evaluate these has not been established in South Africa. We performed an exploratory single-blind trial evaluating a commercial oral-vaginal-combination probiotic as adjunct to SOC for BV treatment. METHODS: Women with symptomatic vaginal discharge were screened for BV and common sexually transmitted infections (STIs). BV+ (Nugent 7-10) but STI- women were randomized to vaginal metronidazole alone (n = 12) or to metronidazole followed by a commercial oral/vaginal probiotic (n = 18). The primary qualitative outcome was to test the regulatory landscape for conducting randomized probiotic trials in South Africa; and acceptability of vaginal application by women. BV cure at 1 month (Nugent≤3) was the primary quantitative endpoint. Secondary quantitative endpoints were BV recurrence, symptoms, vaginal microbiota and genital cytokine changes over 5 months post-treatment. RESULTS: The  South African Health Products Regulatory Authority (SAHPRA) reviewed and approved this trial. As probiotics continue to be regulated as health supplements in South Africa, SAHPRA required a notification application for this trial. Acceptability and adherence to the oral and vaginal application of the probiotic were high, although women reported a preference for oral capsules. 44.8% of women cleared BV one-month post-treatment, and no significant differences in BV cure (RR = 0.52, 95% CI = 0.24-1.16), recurrence, vaginal pH, symptoms, microbiota or vaginal IL-1α concentrations were found between SOC and intervention groups in this pilot study with an over-the-counter product. CONCLUSION: Navigation of the SAHPRA registration process for evaluating a commercial probiotic in a randomised trial laid the foundation for planned larger trials of improved probiotic products for vaginal health in South Africa. Although adherence to the vaginally delivered probiotic was high, women preferred oral application and we recommend that improvements in the content and method of application for future probiotics for vaginal health should be considered. TRIAL REGISTRATION: This trial was registered on 17 October 2017 with the South African National Clinical Trial Register ( http://www.sanctr.gov.za/ ; BV-trial1; DOH-27-1117-5579 ).