Evaluation and Management of Vaginitis.

Vaginitis is a common concern for women across the lifespan. Vaginal symptoms may impact quality of life, and clinicians are challenged in the evaluation and management of bacterial vaginosis, Candida vaginitis, trichomoniasis, desquamative inflammatory vaginitis, and genitourinary syndrome of menopause.

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.

Effect of a yoghurt drink containing Lactobacillus strains on bacterial vaginosis in women - a double-blind, randomised, controlled clinical pilot trial.

Bacterial vaginosis (BV) is characterised by a depletion of lactobacilli in favour of an overgrowth of anaerobic bacteria. It is associated with increased risk for urogenital infections and abortion. In this study we assessed the effect of a yoghurt drink containing Lactobacillus strains on BV. The strains had been isolated from healthy pregnant women and selected for acidification capacity, production of H2O2, glycogen utilisation, bile salt tolerance and inhibition of pathogens. Using Amsel criteria BV was diagnosed in 36 women aged ≥18 years with stable menstrual cycle or menopause. They were treated with oral metronidazole for 7 days (2×500 mg/d). Starting with the treatment, women consumed twice daily either verum or placebo during 4 weeks. Verum was 125 g yoghurt containing (besides Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus) living strains Lactobacillus crispatus LbV 88 (DSM 22566), Lactobacillus gasseri LbV 150N (DSM 22583), Lactobacillus jensenii LbV 116 (DSM 22567) and Lactobacillus rhamnosus LbV96 (DSM 22560), each 1×107 cfu/ml; placebo was 125 g chemically acidified milk. After 4 weeks of intervention 0 of 17 had BV in the verum group versus 6 of 17 in the s.a. control (0.018 in Fisher Exact test). Amsel score decreased during the intervention period by 4.0 (median) (4.0; 3.0) (25th; 75th percentile) in the verum group compared to 2.0 (4.0; 0.0) in the control group (P=0.038 in Mann-Whitney test). Discharge and odour (Amsel criteria 2+3) also decreased by 2.0 (2.0; 1.0) in the verum compared to 1.0 (2.0; 0.0) in the control group (P=0.01) and differed after 4 weeks intervention between the groups 0.0 (0.0; 0.0) versus 1.0 (0.0; 2.0) (P=0.001). Nugent score decreased during the intervention period by 5.5 (7.0;2.3) in the verum compared to 3.0 (6.0;0.5) in the control group (P=0.158). Additional intake of yoghurt containing these probiotic strains improved the recovery rate and symptoms of BV and tended to improve the vaginal microbial pattern.

Probiotics for vaginal health in South Africa: what is on retailers' shelves?

BACKGROUND: Probiotics are widely used to improve gastrointestinal (GI) health, but they may also be useful to prevent or treat gynaecological disorders, including bacterial vaginosis (BV) and candidiasis. BV prevalence is high in South Africa and is associated with increased HIV risk and pregnancy complications. We aimed to assess the availability of probiotics for vaginal health in retail stores (pharmacies, supermarkets and health stores) in two major cities in South Africa. METHODS: A two-stage cluster sampling strategy was used in the Durban and Cape Town metropoles. Instructions for use, microbial composition, dose, storage and manufacturers' details were recorded. RESULTS: A total of 104 unique probiotics were identified in Cape Town and Durban (66.4% manufactured locally). Cape Town had more products than Durban (94 versus 59 probiotics), although 47% were common between cities (49/104). Only four products were explicitly for vaginal health. The remainder were for GI health in adults (51.0%) or infants (17.3%). The predominant species seen overall included Lactobacillus acidophilus (53.5%), L. rhamnosus (37.6%), Bifidobacterium longum ssp. longum (35.6%) and B. animalis ssp. lactis (33.7%). Products for vaginal health contained only common GI probiotic species, with a combination of L. acidophilus/B. longum ssp. longum/B. bifidum, L. rhamnosus/L. reuteri or L. rhamnosus alone, despite L. crispatus, L. gasseri, and L. jensenii being the most common commensals found in the lower female reproductive tract. CONCLUSION: This survey highlights the paucity of vaginal probiotics available in South Africa, where vaginal dysbiosis is common. Most vaginal products contained organisms other than female genital tract commensals.

Papel de los probióticos en Obstetricia y Ginecología / Role of probiotics in obstetrics and gynecology

La microbiota de cada individuo se estima en 2,5-3 kg de peso. La colonización bacteriana comienza en el momento del parto, por contacto del feto con la microbiota vaginal e intestinal de la madre. Los oligosacáridos de la leche materna estimulan el crecimiento de bacterias, que proporcionan el ambiente adecuado para el desarrollo de la inmunidad de la mucosa intestinal. Además, la leche materna es portadora de su propia microbiota, la cual se altera en las mastitis. La vagina constituye otro importante microambiente. Las disbiosis en esta zona conducen a la aparición de vaginosis bacteriana y candidiasis, siendo ambas una patología muy frecuente en la mujer en edad fértil. Los probióticos se presentan como tratamiento potencial y alentador de toda la patología asociada a alteraciones de la microbiota. Son necesarios más estudios que confirmen el beneficio de los probióticos en este campo (AU)

The human microbiota is estimated to be 2.5-3.0 kg. Bacterial colonization starts during delivery, due to fetal contact with vaginal and intestinal maternal microorganisms. The oligosaccharides in human breast milk stimulate the growth of bacteria, which provide the optimal environment for intestinal mucosal immunity development. Additionally, breast milk has its own microbiota and it is altered in mastitis. The vagina is another important microenvironment. Vaginal dysbiosis leads to bacterial vaginosis and vaginal candidiasis, both of them very frequent in reproductive life. The probiotics are a potential and encouraging treatment for all microbiota alterations. Nevertheless, additional studies are required to confirm the benefits of probiotics (AU)

[The role of oral probiotic for bacterial vaginosis in pregnant women. A pilot study]. / Studio pilota sul ruolo dei probiotici nel trattamento della vaginosi batterica in gravidanza.

AIM: The aim of this study was to compare the effects of a dietary supplementation with oral probiotic, and the treatment with vaginal clindamycin in pregnant women with bacterial vaginosis. METHODS: Fourty pregnant women, with a diagnosis of bacterial vaginosis according to the Amsel criteria, were enrolled between the 10th and the 34th week of gestation. The patients were randomized in two groups. Patients in the group A were treated with probiotic orally (VSL3® Ferring), 2 tablets a day for 5 days, followed by 1 tablet daily for 10 days. Patients in group B were treated with vaginal clindamycin 100 mg daily for 15 days. After 5-10 days from the end of the treatment the patients returned for the follow-up. RESULTS: After treatment the vaginal discharge was completely absent in group A, and reduced in group B. The itching occurred only in 10% of patients in each of the two groups. The improvement of constipation occurs only in the group A (P=0.002). Vaginal swabs resulted negative in both groups in particular for Gardnerella V. CONCLUSION: The oral treatment with VSL#3® is effective in the treatment of VB in pregnant women as a topical treatment with clindamycin. In particular for the resolution of leukorrhea, itching and in particular in the bacterial vaginosis caused by Gardnerella V.

Efficacy of orally applied probiotic capsules for bacterial vaginosis and other vaginal infections: a double-blind, randomized, placebo-controlled study.

OBJECTIVE: To assess the efficacy of orally administered capsules containing the probiotics Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 (Lactogyn, JGL, Rijeka, Croatia) compared to placebo in otherwise healthy women diagnosed with bacterial vaginosis. STUDY DESIGN: Randomized, double-blind, multicentric, placebo-controlled trial, including a total of 544 subjects. Included were women older than 18 years of age, diagnosed with vaginal infection. Subjects received either probiotic (395 subjects or 72.6%) or identical-looking placebo capsules (149 subjects or 27.4%,) per day over a period of 6 weeks. Six and 12 weeks after the beginning of the study, subjects underwent two additional gynecological examinations and their vaginal swabs were evaluated by a clinical cytologist. RESULTS: Mean follow-up period after the baseline visit was 44 days. After this period, restitution to balanced vaginal microbiota was reported in 40 subjects (26.9%) in the placebo group, compared to 243 subjects (61.5%) in the probiotic group. Differences between groups were statistically significant at p<0.001. After the additional 6 weeks of follow up, normal vaginal microbiota were still present in more than half (51.1%) of subjects in the probiotic group, but only in around one-fifth (20.8%) of subjects who were taking placebo (p<0.001). CONCLUSION: Oral probiotics could be an alternative, side effect-free treatment for one of the most common indications in gynecology, combining the good aspects of both metronidazole and vaginal capsules.

Efficacy of oral metronidazole with vaginal clindamycin or vaginal probiotic for bacterial vaginosis: randomised placebo-controlled double-blind trial.

BACKGROUND: To determine if oral metronidazole (MTZ-400 mg bid) with 2% vaginal clindamycin-cream (Clind) or a Lactobacillus acidophilus vaginal-probiotic containing oestriol (Prob) reduces 6-month bacterial vaginosis (BV) recurrence. METHODS: Double-blind placebo-controlled parallel-group single-site study with balanced 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. RESULTS: 450 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. CONCLUSION: Combining the recommended first line therapies of oral metronidazole and vaginal clindamycin, or oral metronidazole with an extended-course of a commercially available vaginal-L.acidophilus probiotic, does not reduce BV recurrence. TRIAL REGISTRATION: ANZCTR.org.au ACTRN12607000350426.

Changes in vaginal bacterial concentrations with intravaginal metronidazole therapy for bacterial vaginosis as assessed by quantitative PCR.

Several fastidious bacteria have been associated with bacterial vaginosis (BV) using broad-range bacterial PCR methods such as consensus sequence 16S rRNA gene PCR, but their role in BV remains poorly defined. We describe changes in vaginal bacterial concentrations following metronidazole therapy for BV. Vaginal swabs were collected from women with BV diagnosed using Amsel clinical criteria, and vaginal fluid was assessed by Gram stain to generate Nugent scores. Follow-up swabs were collected 1 month after a 5-day course of vaginal 0.75% metronidazole gel and analyzed for 24 subjects with cured BV and 24 subjects with persistent BV. Changes in bacterial concentrations were measured using eight bacterium-specific 16S rRNA gene quantitative PCR assays. DNA from several fastidious BV-associated bacteria (BVAB) were present at high concentrations in the vagina prior to treatment. Successful antibiotic therapy resulted in 3- to 4-log reductions in median bacterial loads of BVAB1 (P=0.02), BVAB2 (P=0.0004), BVAB3 (P=0.03), a Megasphaera-like bacterium (P<0.0001), Atopobium species (P<0.0001), Leptotrichia/Sneathia species (P=0.0002), and Gardnerella vaginalis (P<0.0001). Median posttreatment bacterial levels did not change significantly in subjects with persistent BV except for a decline in levels of BVAB3. The presence or absence of BV is reflected by vaginal concentrations of BV-associated bacteria such as BVAB1, BVAB2, Leptotrichia/Sneathia species, Atopobium species, Gardnerella vaginalis, and a Megasphaera-like bacterium, suggesting that these bacteria play an important role in BV pathogenesis and may be suitable markers of disease and treatment response.

[Efficacy of Lactobacillus Rhamnosus GR-1 and of Lactobacillus Reuteri RC-14 in the treatment and prevention of vaginoses and bacterial vaginitis relapses]. / Efficacia del Lactobacillus Rhamnosus GR-1 e del Lactobacillus Reuteri RC-14 nel trattamento e nella prevenzione delle recidive nelle vaginosi e nelle vaginiti batteriche.

AIM: The aim of this study was to investigate the efficacy of the use of Lactobacillus rhamnosus GR-1 and of Lactobacillus reuteri RC-14 administrated orally in the treatment and prevention of vaginoses and bacterial vaginitis relapses. METHODS: The study enrolled 50 women in good health, aged between 18 and 48 years, with assessed diagnosis of bacterial vaginosis and vaginitis. The women were randomized in two groups: group A comprised 25 patients with bacterial vaginitis and group B comprised 25 patients with vaginosis. Each patient was administered an antibiotic therapy and subsequently a therapy with Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 (Dicoflor Elle, Dicofarm, Roma, Italy) with two tablets daily for 15 days. After one week from the end of the therapy all patients have been controlled by vaginal swab and microscopic analysis of vaginal secretion. RESULTS: At the end of the study 46 patients had a complete Lactobacilli recolonization, two patients had no colonization and two dropped out. The results showed that 92% of the enrolled patients benefited from the treatment. CONCLUSION: The results of the present study shows that Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, taken orally, were helpful in vaginosis and bacterial vaginitis treatment and in relapse prevention, as they can re-establish the vaginal ecosystem remarkably.

Women's satisfaction with an intravaginal Lactobacillus capsule for the treatment of bacterial vaginosis.

OBJECTIVE: To assess women's satisfaction with a vaginal capsule containing human-derived, H(2)O(2)-producing Lactobacillus crispatus at completion of a randomized, placebo-controlled study for treatment of bacterial vaginosis (BV). METHODS: Women aged 14-35 years with BV were randomized to Lactobacillus or placebo intravaginal capsule twice daily for 3 days monthly for 3 months. Attitudes were assessed with a standardized scale at the final follow-up visit, and associations of satisfaction with clinical and gram stain cure of BV were determined. RESULTS: Four hundred twenty-four women were randomized at enrollment, and 232 (55%) provided data on satisfaction at the final visit. Overall, satisfaction with the capsule was high and was independent of subjects' race, age, and prior history of BV. Report of satisfaction with the capsule, belief that it contained healthy bacteria, and belief that its use improved vaginal health were directly related to clinical cure and to improved Nugent score. Except for women who had BV at the final follow-up visit, most subjects believed that the capsule contained healthy bacteria independent of any outcome reflecting cure. Willingness to use the capsule again was not significantly related to whether subjects experienced clinical cure or normalization of Nugent score at either visit. Adverse effects were rare and were largely related to a perceived difference in vaginal discharge. CONCLUSIONS: Satisfaction with an intravaginal capsule and positive beliefs about its use for BV treatment were prevalent, especially among women with a clinical and microbiological response to BV therapy. However, most women expressed willingness to use the product again regardless of clinical response. Acceptability of and interest in alternative BV treatments, such as L. crispatus intravaginal applications, are high.

In vitro antibacterial activity of Lactobacillus helveticus strain KS300 against diarrhoeagenic, uropathogenic and vaginosis-associated bacteria.

AIMS: The purpose of this study was to investigate in vitro the antibacterial activity of the Lactobacillus helveticus strain KS300 against vaginosis-associated bacteria including Gardnerella vaginalis and Prevotella bivia, uropathogenic Escherichia coli, and diarrhoeagenic Salmonella enterica serovar Typhimurium. METHODS AND RESULTS: The KS300 strain inhibited the growth of G. vaginalis, P. bivia, S. typhimurium, and pathogenic E. coli. After direct co-culture, data show that the Lactobacillus strain decreased the viability of G. vaginalis, P. bivia, S. typhimurium, and pathogenic E. coli. The adhering KS300 strain inhibited the adhesion of G. vaginalis DSM 4944 and uropathogenic Dr-positive E. coli IH11128 onto HeLa cells. Moreover, the KS300 strain inhibited the internalization of uropathogenic Dr-positive E. coli IH11128 within HeLa cells and S. typhimurium SL1344 within Caco-2/TC7 cells. CONCLUSIONS: The findings demonstrate that L. helveticus strain KS300 is adhesive onto cultured human cells and has antagonistic activities against vaginosis-associated, uropathogenic and diarrhoeagenic pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: Adhering L. helveticus strain KS300 is a potential probiotic strain displaying a strain-specific array of in vitro antibacterial activities.