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Lactobacillus, in vaginitis [keywords]
- Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor(®)) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. [JOURNAL ARTICLE]
- Breast Cancer Res Treat 2014 Apr 10.
Phase I pharmacokinetic (PK) study assessed circulating estrogens in breast cancer (BC) patients on a non-steroidal aromatase inhibitor (NSAI) with vaginal atrophy using vaginal ultra-low-dose 0.03 mg estriol (E3) and Lactobacillus combination vaginal tablets (Gynoflor(®)). 16 women on NSAI with severe vaginal atrophy applied a daily vaginal tablet of Gynoflor(®) for 28 days followed by a maintenance therapy of 3 tablets weekly for 8 weeks. Primary outcomes were serum concentrations and PK of E3, estradiol (E2), and estrone (E1) using highly sensitive gas chromatography-mass spectrometry. Secondary outcomes were clinical measures for efficacy and side effects; microscopic changes in vaginal epithelium and microflora; and changes in serum FSH, LH, and sex hormone-binding globulin. Compared with baseline, serum E1 and E2 did not increase in any of the women at any time following vaginal application. Serum E3 transiently increased after the first application in 15 of 16 women, with a maximum of 168 pg/ml 2-3 h post-insertion. After 4 weeks, serum E3 was slightly increased in 8 women with a maximum of 44 pg/ml. The vaginal atrophy resolved or improved in all women. The product was well tolerated, and discontinuation of therapy was not observed. The low-dose 0.03 mg E3 and Lactobacillus acidophilus vaginal tablets application in postmenopausal BC patients during AI treatment suffering from vaginal atrophy lead to small and transient increases in serum E3, but not E1 or E2, and therefore can be considered as safe and efficacious for treatment of atrophic vaginitis in BC patients taking NSAIs.
- Probiotics in the prevention of recurrences of bacterial vaginosis. [Journal Article, Review]
- Altern Ther Health Med 2014.:52-7.
Bacterial vaginosis (BV) is the most common cause of vaginal discharge in women during their fertile years. BV prevalence runs from 10%-50%, in part due to the high rate of recurrence after standard treatment. Women with BV may experience a decreased quality of life and are at risk of serious obstetric complications. Limited data are available regarding optimal management strategies for preventing recurrence of BV, emphasizing the importance of the availability of a comprehensive source of scientific information and therapeutic strategies.The aim of this study was to evaluate the frequency and clinical relevance of the recurrence of BV and to collect and review data about prophylactic approaches based on probiotic supplementation with lactobacilli (LB).A review of the literature was performed, based on combinations of the following keywords: bacterial vaginosis, bacterial vaginosis recurrences, vaginal discharge, vaginal flora, LB, Lactobacillus rhamnosus, and probiotic supplementation.The studies were evaluated in terms of the cure rates for BV, incidence of recurrence of BV, decrease in patients' discomfort, maintenance of a healthy vaginal recolonization, and occurrence of complications and side effects.Recurrence of BV after standard therapy is a relevant clinical problem, with an incidence of 30%-40% and a significant impact on women's quality of life and on their risk of infrequent but serious obstetric complications. Therefore, finding effective prophylactic therapies to avoid or decrease the recurrence of BV is important. Even when they are effective, typical antibacterial regimens for long-term maintenance are known to have side effects. Different schemes of treatment with exogenous LB have proven effective in preventing recurrence of BV, even in patients at high risk for relapse.Probiotic supplementation with vaginal LB proved to be crucial in hindering bacteria growth after antibiotic therapy; therefore this intervention may be considered a new adjuvant treatment for preventing recurrence of BV, even in high-risk patients.
- Bacteria in the Vaginal Microbiome Alter the Innate Immune Response and Barrier Properties of the Human Vaginal Epithelia in a Species-Specific Manner. [JOURNAL ARTICLE]
- J Infect Dis 2014 Feb 12.
Background. Bacterial vaginosis increases the susceptibility to sexually transmitted infections and negatively affects women's reproductive health.Methods. To investigate host-vaginal microbiota interactions and the impact on immune barrier function, we colonized 3-dimensional (3-D) human vaginal epithelial cells with 2 predominant species of vaginal microbiota (Lactobacillus iners and Lactobacillus crispatus) or 2 prevalent bacteria associated with bacterial vaginosis (Atopobium vaginae and Prevotella bivia).Results. Colonization of 3-D vaginal epithelial cell aggregates with vaginal microbiota was observed with direct attachment to host cell surface with no cytotoxicity. A. vaginae infection yielded increased expression membrane-associated mucins and evoked a robust proinflammatory, immune response in 3-D vaginal epithelial cells (ie, expression of CCL20, hBD-2, interleukin 1β, interleukin 6, interleukin 8, and tumor necrosis factor α) that can negatively affect barrier function. However, P. bivia and L. crispatus did not significantly upregulate pattern-recognition receptor-signaling, mucin expression, antimicrobial peptides/defensins, or proinflammatory cytokines in 3-D vaginal epithelial cell aggregates. Notably, L. iners induced pattern-recognition receptor-signaling activity, but no change was observed in mucin expression or secretion of interleukin 6 and interleukin 8.Conclusions. We identified unique species-specific immune signatures from vaginal epithelial cells elicited by colonization with commensal and bacterial vaginosis-associated bacteria. A. vaginae elicited a signature that is consistent with significant disruption of immune barrier properties, potentially resulting in enhanced susceptibility to sexually transmitted infections during bacterial vaginosis.
- Benzoyl peroxide formulated polycarbophil/carbopol 934P hydrogel with selective antimicrobial activity, potentially beneficial for treatment and prevention of bacterial vaginosis. [Journal Article]
- Infect Dis Obstet Gynecol 2013.:909354.
The human vagina is colonized by a variety of indigenous microflora; in healthy individuals the predominant bacterial genus is Lactobacillus while those with bacterial vaginosis (BV) carry a variety of anaerobic representatives of the phylum Actinobacteria. In this study, we evaluated the antimicrobial activity of benzoyl peroxide (BPO) encapsulated in a hydrogel against Gardnerella vaginalis, one of the causative agents of BV, as well as indicating its safety for healthy human lactobacilli. Herein, it is shown that in well diffusion assays G. vaginalis is inhibited at 0.01% hydrogel-encapsulated BPO and that the tested Lactobacillus spp. can tolerate concentrations of BPO up to 2.5%. In direct contact assays (cells grown in a liquid culture containing hydrogel with 1% BPO or BPO particles), we demonstrated that hydrogels loaded with 1% BPO caused 6-log reduction of G. vaginalis. Conversely, three of the tested Lactobacillus spp. were not inhibited while L. acidophilus growth was slightly delayed. The rheological properties of the hydrogel formulation were probed using oscillation frequency sweep, oscillation shear stress sweep, and shear rate sweep. This shows the gel to be suitable for vaginal application and that the encapsulation of BPO did not alter rheological properties.
- [Effect of IL-1beta on growth properties of vaginal microsymbionts]. [English Abstract, Journal Article]
- Zh Mikrobiol Epidemiol Immunobiol 2013 Jul-Aug; (4):65-9.
Study the effect of IL-1beta in concentrations that are characteristic for vaginal normo- and pathocenosis on growth properties of vaginal microsymbionts.Concentration of IL-1beta in vaginal contents of women during bacterial vaginosis and normocenosis was determined by using enzume immunoassay. Changes of growth characteristics and biofilm formation ability of Staphylococcus aureus, Escherichia coli, Lactobacilus spp., Corynebacterium spp. under the effect of various IL-1beta concentrations by method of O'Toole G.A. (1999) were studied.IL-1beta in concentrations characteristic for normocenosis was shown to be able to cause stimulating effect on growth properties of lactobacilli and corynebacteria and suppress growth of S. aureus and E. coli in both plankton and biofilm cultures. IL-1beta concentrations characteristic for vaginal dysbiosis on the contrary result in suppression of growth of lactobacilli biomass against the background of stimulation of growth properties and biofilm formation ability of S. aureus and E. coli.Differential dose-dependent effect of IL-1beta on biomass growth and biofilm formation ability of vaginal microsymbionts is a mechanism of regulation of vaginal microbiocenosis.
- More than meets the eye: associations of vaginal bacteria with gram stain morphotypes using molecular phylogenetic analysis. [Journal Article, Research Support, N.I.H., Extramural]
- PLoS One 2013; 8(10):e78633.
Bacterial vaginosis (BV) is a highly prevalent condition associated with adverse health outcomes. Gram stain analysis of vaginal fluid is the standard for confirming the diagnosis of BV, wherein abundances of key bacterial morphotypes are assessed. These Lactobacillus, Gardnerella, Bacteroides, and Mobiluncus morphotypes were originally linked to particular bacterial species through cultivation studies, but no studies have systematically investigated associations between uncultivated bacteria detected by molecular methods and Gram stain findings. In this study, 16S-rRNA PCR/pyrosequencing was used to examine associations between vaginal bacteria and bacterial morphotypes in 220 women with and without BV. Species-specific quantitative PCR (qPCR) and fluorescence in Situ hybridization (FISH) methods were used to document concentrations of two bacteria with curved rod morphologies: Mobiluncus and the fastidious BV-associated bacterium-1 (BVAB1). Rank abundance of vaginal bacteria in samples with evidence of curved gram-negative rods showed that BVAB1 was dominant (26.1%), while Mobiluncus was rare (0.2% of sequence reads). BVAB1 sequence reads were associated with Mobiluncus morphotypes (p<0.001). Among women with curved rods, mean concentration of BVAB1 DNA was 2 log units greater than Mobiluncus (p<0.001) using species-specific quantitative PCR. FISH analyses revealed that mean number of BVAB1 cells was 2 log units greater than Mobiluncus cells in women with highest Nugent score (p<0.001). Prevotella and Porphyromonas spp. were significantly associated with the "Bacteroides morphotype," whereas Bacteroides species were rare. Gram-negative rods designated Mobiluncus morphotypes on Gram stain are more likely BVAB1. These findings provide a clearer picture of the bacteria associated with morphotypes on vaginal Gram stain.
- [Effect of Lactobacillus casei var rhamnosus (Gynophilus) in restoring the vaginal flora by female patients with bacterial vaginosis--randomized, open clinical trial]. [English Abstract, Journal Article, Randomized Controlled Trial]
- Akush Ginekol (Sofiia) 2013.:48-53.
The vaginal probiotics can increase the clinical and microbiological efficacy of the therapeutic regimens used for the treatment of bacterial vaginosis. The Aim of our study was to evaluate the effect of the application of Lactobacillus casei var rhamnosus (Gynophilus--probiotic species Lcr 35) in restoring the vaginal flora and prevention of relapses by female patients with anaerobic vaginal infection undergoing conventional (nitroimidazole) local and main therapy.In the study were included 60 women with established Amsel/Nugent bacterial vaginosis who were randomized in two groups. The first group patients (n-30 beginning/n-25 controls) underwent a 5 day treatment with two daily peroral doses of metronidazole 500 mg, with local application of metronidazole ovules 1000 mg at the 1st and the 3rd day (M+M). In the second group (n-30 beginning/n-26 controls) the therapeutic regimen was the same as in the first group, with additional 7 day treatment with Lactobacillus casei var rhamnosus - Lcr 35. (Gynophilus) vaginal ovules, two daily doses (M+M+G).30% to 40% was the difference/enhance of the clinical efficacy according to the clinical indicators when Lactobacillus casei var rhamnosus - Lcr 35 was added to the standard nitroimidazole therapy. Concerning the main clinical indicator: Amsel criteria, the improvement after the therapy in the first group (M+M) was 60% (n-15) and in the second group (M+M+G) 88.5% (n-23). According to the microbiological indicators the improvement in the first group (M+M) based on the vaginal flora evaluation (Nugent score) was 60% (n-15) and in the second group, after the addition of Lcr 35 it was 88.5% (n-23).The application of Gynophilus after conventional 5-nitroimidazole treatment for bacterial vaginosis increased the clinical and microbiological efficacy of the therapy by 25% - 30%. The microbial balance in the vaginal ecosystem was restored in the majority of patients (88%), which is a prerequisite for low percentage of bacterial vaginosis relapses.
- [Probiotic monotherapy of bacterial vaginosis: a open, randomized trial]. [English Abstract, Journal Article, Randomized Controlled Trial]
- Akush Ginekol (Sofiia) 2013.:36-42.
The aim of the current research is to establish the clinical and microbiological efficacy of the therapy with local probiotics in the treatment of anaerobic vaginal infections and the therapy's effect upon vaginal flora.381 (100%) women with bacterial vaginitis are included in the research. They were randomized into three groups. In the first group 143 women who were treated with local (10 applications) probiotics vaginal medicine, containing live lactobacillus types Lactobacillus acidophilus, Lactobacillus rhamnosus. In the second group 126 patients were treated with five days oral administration of Clindamycin (tabl.x 600 mg) BID and local therapy of two vaginal ovules containing each 1000 mg Metronidazole, which were administered intravaginal every other day. In the third group 112 women were treated with the same therapy as the second group and in addition started from the day 5 after it were administered locally probiotic medicine containing Lactobacillus acidophilus u Lactobacillus rhamnosus. The efficacy of the therapeutic scheme was evaluated via comparison of patients' clinical complains in the different groups, of data from clinical examinations (Amsel) and microbiological tests (Nugent) for each patient.Thirty five-forty days after the probiotic therapy, the clinical efficacy in this group (Amsel) is 42.7% and microbiological efficacy (Gram preparation - Nugent)--41.3%. They are lower than the results which we received in the groups where the combine nitroimidazole/incozamide treatment was performed with or without local probiotic. The second group: clinical efficacy--51.6%, microbiological (Nugent)--46.4%. The highest clinical--87.5% and microbiological--80.3% efficacy showed the combine nitroimidazole/lincozamide/probiotic treatment in the third group.Our results show that the local monotherapy with probiotics has fewer efficacies in comparison to the combine therapeutic schemes for treatment of vaginal disbacteriosis with dominant anaerobic species.
- [Efficacy of combined 5-nitroimidazole and probiotic therapy of bacterial vaginosis: randomized open trial]. [English Abstract, Journal Article, Randomized Controlled Trial]
- Akush Ginekol (Sofiia) 2013; 52(3):19-26.
The aim of the current research is to identify the clinical and microbiological effect of 5-nitroimidazol therapy for the treatment of bacterial vaginosis and in combination with probiotics and the influence of such therapy upon vaginal flora.Women (n = 539) with bacterial vaginosis who meet the criteria were included in the study. They were randomized into two groups with the following therapeutic regimes: in the first group (n = 242 women) the treatment included applications of 2g BID tinidazole for two days and vaginal suppositories of 1000 mg metronidazol at day 1 and 3 (T+M). In the second group (n = 297) the women were cured with the same treatment as those in the first group. In addition to it from the fifth day of the treatment was added a topical administration of vaginal probiotic which contains species of alive lactobacilli: Lactobacillus acidophilus, Lactobacillus rhamnosus (T+M+P). The efficacy from the therapy was evaluated using the clinical compliances of the women, the data from the clinical examination and the microbiological tests results.The results showed expected increase of clinical therapy efficacy (Amsel - criteria) from 42.8% (T+M; n = 211/242) to 84.06% (T+M+P; n = 274/297) in groups and of microbiological efficacy (Nugent) from 44.7% (T+M; n = 211/242) to 83.3% (T+M+P; n = 274/297), in follow up 35-40 days from the beginning of treatment. The percentage of women with normal vaginal flora on 35-40 day after the therapy increase with 57% in the (T+M) first group while in the second group (T+M+P) with 94%.Combining the therapies of 5-nitroimidazoles and vaginal probiotic reduce bacterial vaginosis recurrence and restores permanently normal vaginal flora.
- Prevalence of Gardnerella vaginalis among women with lactobacillus-predominant vaginal flora. [Journal Article]
- Sex Transm Infect 2014 Feb; 90(1):61-3.
To determine the prevalence of Gardnerella vaginalis in women with normal vaginal flora.Women without symptoms or signs of vaginal infection and five or fewer lifetime sexual partners were recruited for a longitudinal study of vaginal flora. Negative Amsel criteria and a Nugent score of 0-3 were required for enrolment. Vaginal specimens were self-collected daily for Gram stain and every 3 days for PCR for G vaginalis for 30 days. Women completed daily diaries recording sexual activity, symptoms and menses.Twenty women were recruited for the study with 19 completing all specimens and 1 lost to follow-up. During the 30-day study period, 13/19 (68.4%) of women had normal Nugent scores (0-3) whereas 6/19 (31.6%) of women had at least 2 days of Nugent scores in the intermediate range (p=0.09). Among the 19 women, 9 (47%) were negative for G vaginalis by PCR throughout the study period whereas 10 (53%) had at least one specimen that demonstrated the presence of G vaginalis by PCR. Of those women with intermediate flora on Gram stain during the course of the study 5/6 (83.3%) were positive for G vaginalis while 5/13 (38.5%) of those women with only normal Nugent scores were positive for G vaginalis. Thus, 61.5% of women with normal Nugent scores had no evidence of G vaginalis by serial PCR.Gardnerella may not be part of the normal flora in women with optimal vaginal health.