Bacteriocin production of the probiotic Lactobacillus acidophilus KS400.

In the last years, the use of probiotics, including Lactobacillus species, has received much attention to prevent and treat vaginal disorders. These species have been described as having the ability to colonize the epithelial surface and produce antimicrobial metabolites that are able to control the remaining vaginal microflora. This study aimed to identify and characterize, for the first time, a bacteriocin natively produced by Lactobacillus acidophilus KS400 (probiotic strain from Gynoflor®-Medinova AG, Switzerland) and its antimicrobial activity against relevant urogenital pathogens. After organic acids and hydrogen peroxide neutralization in the fermented Lactobacillus acidophilus KS400 culture medium, bacteriocin activity was tested against the indicator microorganism Lactobacillus delbrueckii ATCC9649. The fermentation of Lactobacillus acidophilus KS400 for bacteriocin production was carried out in batch mode, and its antimicrobial activity, optical density and pH were monitored. After production and extraction, the bacteriocin molecular weight was estimated by electrophoresis and tested against vaginal pathogenic microorganisms. As described for other bacteriocins, batch fermentation profiles indicated that bacteriocin production occurs during the exponential growth phase of the lactobacilli, and declines during their stationary growth phase. The molecular weight of the bacteriocin is approximately 7.5 kDa. The bacteriocin containing protein extract was shown to inhibit the growth of Gardnerella vaginalis, Streptococcus agalactiae, Pseudomonas aeruginosa and the indicator strain Lactobacillus delbrueckii ATCC9649. We conclude that L. acidophilus KS400 produces bacteriocin with antimicrobial activity against relevant urogenital pathogens.

VALHUDES: A protocol for validation of human papillomavirus assays and collection devices for HPV testing on self-samples and urine samples.

BACK GROUND: Systematic reviews have concluded that hrHPV DNA testing using target-amplification tests is as accurate on vaginal self-samples as on clinician-taken specimens for the detection of cervical precancer. However, insufficient evidence is available for specific HPV assay/self-sample device combinations. OBJECTIVES: The VALHUDES protocol is designed as a diagnostic test accuracy study that aims to compare the clinical sensitivity and specificity of particular hrHPV assay(s) on vaginal self-samples and first-void-urine, collected in agreement with standardized protocols, with hrHPV testing on matched clinician-taken samples. STUDY DESIGN: Five hundred enrolled women referred to a colposcopy clinic are invited to collect a first-void urine sample and one or more vaginal self-samples with particular devices before collection of a cervical sample by a clinician. Sample sets are subsequently analysed in a laboratory accredited for HPV testing. Disease verification for all enrolled patients is provided by colposcopy combined with histological assessment of biopsies. RESULTS: A first VALHUDES study has started in Belgium in December 2017 with enrolment from four colposcopy centres. The following assays are foreseen to be evaluated: RealTime High Risk HPV assay (Abbott), cobas-4800 and -6800 (Roche), Onclarity (BD), Xpert HPV (Cepheid) and Anyplex II HPV HR (Seegene). CONCLUSION: Given empirical evidence that the relative accuracy of HPV-testing on self- vs clinician-samples is robust across clinical settings, the VALHUDES protocol offers a framework for validation of HPV assay/self-sample device combinations that can be translated to a primary screening setting.

Should we be testing for urogenital Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum in men and women? - a position statement from the European STI Guidelines Editorial Board.

At present, we have no evidence that we are doing more good than harm detecting and subsequently treating Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum colonizations/infections. Consequently, routine testing and treatment of asymptomatic or symptomatic men and women for M. hominis, U. urealyticum and U. parvum are not recommended. Asymptomatic carriage of these bacteria is common, and the majority of individuals do not develop any disease. Although U. urealyticum has been associated with urethritis in men, it is probably not causal unless a high load is present (likely carriage in 40-80% of detected cases). The extensive testing, detection and subsequent antimicrobial treatment of these bacteria performed in some settings may result in the selection of antimicrobial resistance, in these bacteria, 'true' STI agents, as well as in the general microbiota, and substantial economic cost for society and individuals, particularly women. The commercialization of many particularly multiplex PCR assays detecting traditional non-viral STIs together with M. hominis, U. parvum and/or U. urealyticum has worsened this situation. Thus, routine screening of asymptomatic men and women or routine testing of symptomatic individuals for M. hominis, U. urealyticum and U. parvum is not recommended. If testing of men with symptomatic urethritis is undertaken, traditional STI urethritis agents such as Neisseria gonorrhoeae, Chlamydia trachomatis, M. genitalium and, in settings where relevant, Trichomonas vaginalis should be excluded prior to U. urealyticum testing and quantitative species-specific molecular diagnostic tests should be used. Only men with high U. urealyticum load should be considered for treatment; however, appropriate evidence for effective treatment regimens is lacking. In symptomatic women, bacterial vaginosis (BV) should always be tested for and treated if detected.

Improvement of abnormal vaginal flora in Ugandan women by self-testing and short use of intravaginal antimicrobials.

The vaginal composition of African women is more often lactobacillus-deficient compared to that of women from other areas around the world. Lactobacillus-deficient microflora is a known risk factor for serious health problems, such as preterm birth, cervix cancer, and entrapment of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). The aim of this study was to assess the effect of local vaginal antibiotic or antiseptic treatment on abnormal vaginal flora (AVF), aerobic vaginitis (AV), and bacterial vaginosis (BV) among women in rural, semi-urban, and urban areas in Uganda, as compared to placebo. In a double-blind, placebo-controlled, randomized trial, 300 women presenting for outpatient routine, follow-up, or medical care at Mulago Hospital in Kampala, Uganda, were enrolled to receive 6 days of treatment with vaginal rifaximin (RFX), dequalinium chloride (DQC), or placebo if they had an increased vaginal pH of >4.5 as determined by self-testing. At initial visit and at control visit after 4 weeks, a smear was taken for blinded wet mount microscopy to determine AVF, BV, AV, and Candida severity scores. As compared to placebo, both RFX or DQC treatments dramatically diminished BV prevalence and severity from the initial to follow-up visit: the BV score declined from 2.5 to 1.6 (p < 0.0001) and from 2.5 to 1.9 (p < 0.0001), respectively. Similarly, strong improvements in the AV score were seen in both treatment regimens: moderate and severe AV declined from AV scores of 6.3 to 3.6 (p = 0.003) and from 6.6 to 4.1 (p < 0.004), respectively. Also, women with AVF (deceased or absent lactobacilli) showed similar improvements when compared with placebo. Women with normal flora and Candida at the initial visit showed less Candida after 4 weeks in the group treated with DQC (p = 0.014). Even after a short duration of intravaginal treatment with local non-absorbable antiseptics or antibiotics produced significant, lasting improvements in the vaginal microbiome composition of women with disturbed vaginal microflora. As African women have high prevalences of BV, AV, and AVF, this approach could improve their odds to prevent health-compromising complications. Further studies assessing direct health outcomes are needed to substantiate this.

Influence of contraceptive choice on vaginal bacterial and fungal microflora.

The influence of contraception on vaginal microflora can have a major impact on the risk of developing acute or recurrent vaginal infections, but also may influence the risk of acquiring sexually transmissible infections (STI) such as HIV. A cohort of 248 women presenting for levonorgestrel-releasing intrauterine system (LNG-IUS) insertion or reinsertion were stratified according to their current contraceptive method. Information concerning their menstrual pattern and data about the medical history were collected. The composition of their vaginal microflora was studied by detailed phase contrast microscopy of fresh vaginal fluid, and aerobic cultures were taken to detect enteric bacterial growth and fungal colonisation. LNG-IUS and progesterone-only-pill (POP) users had significantly lower blood loss (p < 0.001) than other women. Regardless of the type of contraception used, all women reported similar rates of symptomatic lower genital tract infection during the preceding year. Women using combined oral contraception (COC) and long-term LNG-IUS had the same bacterial composition of vaginal microflora as non-contraceptive users, even when infections were combined. Both hormonal and non-hormonal intrauterine device users had an increased tendency to have more vaginal colonisation with Candida. Women on POPs or subcutaneous implants had a tendency towards increased vaginal atrophy, but had a lower Candida carriage rate compared to IUCD users (LNG-IUS and Copper-IUCD, p = 0.037). Women with an increased risk of acquiring STIs or recurrent BV could benefit from LNG-IUS or COC due to a well-preserved vaginal bacterial flora. Women with a susceptibility for RVVC should prefer POPs, and avoid intrauterine contraception.

Increased vaginal pH in Ugandan women: what does it indicate?

Abnormal vaginal flora (AVF), indicative of bacterial vaginosis (BV) and/or aerobic vaginitis (AV), amongst other abnormalities, is a risk factor for multiple complications in pregnant as well as non-pregnant women. Screening for such conditions could help prevent these complications. Can self-testing for increased vaginal pH reliably detect BV and other high-risk microflora types, and is this more accurate than performing Gram stain-based Nugent score when screening for high-risk microflora? A total of 344 women presenting at different outpatient clinics in Mulago Hospital and Mbuikwe Outpatient clinics in Kampala, Uganda, were asked to test themselves by introducing a gloved finger into the vagina and smearing it on a microscopy slide, on which a pH strip was attached. Self-assessed categories of normal (pH 3.6-4.4), intermediate (4.5-4.7) or high pH (>4.7) were compared with demographic and with centralised microscopic data, both in air-dried rehydrated wet mounts (Femicare), as well as in Gram-stained specimens (Nugent). AVF was present in 38 %, BV in 25 % and AV in 11 % of patients. High pH and AVF is correlated with human immunodeficiency virus (HIV), infertility, frequent sex, but not vaginal douching. Screening for raised pH detects 90 % of AVF cases, but would require testing over half of the population. As AV and non-infectious conditions are frequent in women with AVF and high pH, Nugent score alone is an insufficient technique to screen women for a high-risk vaginal microflora, especially in infertile and HIV-infected women.

Bacterial vaginosis, aerobic vaginitis, vaginal inflammation and major Pap smear abnormalities.

The purpose of this investigation was to evaluate the impact of the vaginal milieu on the presence of abnormal Pap smears and a positive human papilloma virus (HPV) test. A cross-sectional study was conducted between June 2014 and May 2015, evaluating the vaginal discharge by fresh wet mount microscopy and comparing these data with Pap smear findings. Wet mount slides were scored for bacterial vaginosis (BV), aerobic vaginitis (AV), presence of Candida and Trichomonas vaginalis. Cytologic evaluation was done on all Pap smears according to the Bethesda criteria. The cobas© HPV Test (Roche) was performed for HPV detection. A total of 622 cases were evaluated. The mean age of the patients was 41.6 ± 10.65 years (range 21-75). Eighty-three women (13.3 %) had a cytology result worse than low-grade squamous intraepithelial lesion (LSIL). When comparing this group with the one with normal or minor [atypical squamous cells of undetermined significance (ASC-US) or LSIL] Pap smear abnormalities, there were no differences in the presence of Candida (32.5 % vs. 33.2 %, p = 1.0), absence of lactobacilli (38.6 % vs. 32.5 %, p = 0.32) or BV (20.5 % vs. 13.2 %, p = 0.09). On the other hand, moderate or severe inflammation (msI) (41.0 % vs. 28.8 %, p = 0,04), moderate or severe AV (msAV) (16.9 % vs. 7.2 %, p = 0.009) and msAV/BV (37.3 % vs. 20.0 %, p = 0.001) were more common in women with such major cervical abnormalities. No significant association was found between deviations of the vaginal milieu and high-risk HPV infection. The presence of msI or msAV, but not BV, is independently associated with an increased risk of major cervical cytological abnormalities, but not with HPV infection.

Diagnosis of aerobic vaginitis by quantitative real-time PCR.

PURPOSE: To evaluate a real-time PCR-based technique to quantify bacteria associated with aerobic vaginitis (AV) as a potential test. METHODS: Vaginal samples from 100 women were tested by wet-mount microscopy, gram stain and quantitative real-time PCR targeting Enterobacteriacea, Staphylococcus spp., Streptococcus spp., Enterococcus spp., Escherichia coli, Streptococcus agalactiae, S. aureus; Lactobacillus spp. AV diagnosis obtained by wet-mount microscopy was used as reference. RESULTS: Some level of AV was diagnosed in 23 (23.7 %) cases. Various concentrations of Enterobacteriacea, Staphylococcus spp., Streptococcus spp. were detected an all patients. Enterococcus spp. were detected in 76 (78.3 %) cases. Summarized concentrations of aerobes were tenfold higher in AV-positive compared to AV-negative cases [7.30lg vs 6.06lg (p = 0.02)]. Concentrations of aerobes in severe, moderate and light AV cases did not vary significantly (p = 0.14). Concentration of lactobacilli was 1000-fold lower in AV-positive cases compared to normal cases (5.3lg vs 8.3lg, p < 0.0001). Streptococcus spp. dominated in the majority of AV-positive cases [19/22 (86.4 %) samples]. The relation of high loads of aerobes to the low numbers of Lactobacilli are a reliable marker for the presence of AV and could substitute microscopy as a test. CONCLUSIONS: PCR may be a good standardized substitution for AV diagnosis in settings where well-trained microscopists are lacking.

Vaginal microbiome and metabolome highlight specific signatures of bacterial vaginosis.

In this study, we sought to find novel bacterial and metabolic hallmarks for bacterial vaginosis (BV). We studied the vaginal microbiome and metabolome of vaginal fluids from BV-affected patients (n = 43) and healthy controls (n = 37) by means of an integrated approach based on quantitative polymerase chain reaction (qPCR) and proton nuclear magnetic resonance ((1)H-NMR). The correlations between the clinical condition and vaginal bacterial communities were investigated by principal component analysis (PCA). To define the metabolomics signatures of BV, 100 discriminant analysis by projection on latent structure (PLS-DA) models were calculated. Bacterial signatures distinguishing the health condition and BV were identified by qPCR. Lactobacillus crispatus strongly featured the healthy vagina, while increased concentrations of Prevotella, Atopobium and Mycoplasma hominis specifically marked the infection. (1)H-NMR analysis has led to the identification and quantification of 17 previously unreported molecules. BV was associated with changes in the concentration of metabolites belonging to the families of amines, organic acids, short chain fatty acids, amino acids, nitrogenous bases and monosaccharides. In particular, maltose, kynurenine and NAD(+) primarily characterised the healthy status, while nicotinate, malonate and acetate were the best metabolic hallmarks of BV. This study helps to better understand the role of the vaginal microbiota and metabolome in the development of BV infection. We propose a molecular approach for the diagnosis of BV based on quantitative detection in the vaginal fluids of Atopobium, Prevotella and M. hominis, and nicotinate, malonate and acetate by combining qPCR and (1)H-NMR.

Effect of ultra-low-dose estriol and lactobacilli vaginal tablets (Gynoflor®) on inflammatory and infectious markers of the vaginal ecosystem in postmenopausal women with breast cancer on aromatase inhibitors.

This study was a detailed microscopic analysis of the changes of vaginal microflora characteristics after application of 0.03 mg estriol-lactobacilli combination on the vaginal ecosystem in postmenopausal breast cancer (BC) survivors on aromatase inhibitors (AI) with severe atrophic vaginitis. A total of 16 BC women on AI applied daily one vaginal tablet of Gynoflor® for 28 days followed by a maintenance therapy of three tablets weekly for 8 weeks. During four follow up visits a smear from the upper lateral vaginal wall was analysed by phase contrast microscopy at 400 times magnification in order to classify the lactobacillary grades(LBG), bacterial vaginosis (BV), aerobic vaginitis (AV), vulvovaginal candidosis (VVC), proportional number of leukocytes and evidence of parabasal cells and epitheliolysis. LBG improved from 81% LBG-III at entry to 88% LBG-I&IIa after 2 weeks of initial therapy, which further improved upon follow up (p < 0.001). Whereas BV was a rare event, AV was frequent and substantially improved during treatment (p < 0.01). While at entry most patients had moderate or severe AV, after maintenance therapy no patient except one had AV. The number of leukocytes dropped dramatically from a score of 1.78 ± 0.70 to 1.06 ± 0.25 which was consistent till the end of the study (p < 0.01). Parabasal cells dropped from a score of 3.4 ± 0.64 at entry to 1.3 ± 0.60 at the final visit (p trend < 0.01). Starting from a low rate of Candida colonisation of 2/14 (14%), a sudden rise to 7/16 (44%) occurred after 2 weeks, to return back to base levels at subsequent visits. The vaginal use of ultra-low dose estriol and lactobacilli results in rapid and enduring improvement of all markers of the vaginal microflora and epithelial vaginal cell quality in women with breast cancer on AI with dyspareunia. Candida may develop soon after its use, but rapidly disappears again upon their prolonged use. Due to its excellent safety profiles and clinical efficacy we recommend this product as first choice in women on AI with severe dyspareunia.

Vaginal estriol-lactobacilli combination and quality of life in endocrine-treated breast cancer.

OBJECTIVE: We investigated the effect of a combination of vaginal ultra-low-dose estriol with lactobacilli on the sexual functioning domain of quality of life during the treatment of breast cancer survivors on an aromatase inhibitor with vaginal atrophy. SUBJECTS AND METHODS: This was an open-label, bicentric, exploratory, clinical study in 16 postmenopausal breast cancer survivors on aromatase inhibitors suffering from vaginal atrophy-induced sexual disorders. Atrophy symptoms were assessed by scoring with an 11-point estimation scale (0 = not at all, 10 = worst imaginable feeling). Sexuality parameters of quality of life and medication adherence were recorded in a patient's diary and in the Female Somatic Sexual Experience Instrument (FSSEI) questionnaire. Patients underwent an initial treatment for 4 weeks (one vaginal tablet of Gynoflor(®) containing 0.03 mg estriol daily), followed by maintenance therapy (three vaginal Gynoflor(®) tablets weekly) for 8 weeks. RESULTS: Vaginal dryness continuously improved from a median score of 8 at entry to a score of 4 at the end of initial therapy, and a median score of 2 at the end of maintenance therapy. Normal sexual activity before breast cancer diagnosis was reported by 14 women (88%). At study entry, only three women (19%) were sexually active. At the end of the Gynoflor(®) regimen, ten women (63%) reported sexual activity, of which seven (44%) reported sexual intercourse. The FSSEI demonstrated a non-significant trend of improvement of parameters related to sexuality. CONCLUSIONS: Local vaginal therapy with Gynoflor(®) in breast cancer survivors on aromatase inhibitors reporting atrophic vaginitis could be considered as a useful treatment for the quality of sexual life.

[The use of intrauterine device in nulliparous over 18 years: a Belgian consensus]. / La contraception intra-utérine chez la nultlipare de plus de 18 ans: vers un consensus belge.

Under the presidency of prof. H. Depypere (UZ Ghent) and Prof. P. Simon (ULB Erasme) a Belgian panel of thirteen experts (gynecologists, representatives of universities and scientific associations for gynecology-obstetrics) reached a consensus on the use of intrauterine systems, both copper IUDs as hormone IUDs, in nultiparous women.

Multiple human papillomavirus infections and HIV seropositivity as risk factors for abnormal cervical cytology among female sex workers in Nairobi.

We estimated type-specific prevalence of human papillomavirus (HPV) and examined risk factors for abnormal cervical cytology among 296 female sex workers from Nairobi, Kenya. Over half (54%) were infected with a high-risk (HR) HPV type, of which HPV16 and 52 were the most common types. HIV-1 prevalence was 23% and HIV-1 sero-positivity was associated with high-grade cervical lesions, particularly among women with CD4 count less than 500 cells/mm(3) (odds ratio [OR] = 6.9; 95% confidence interval [CI]: 1.7-24.9). Among women who had normal cytology at the time of entry into the study, the risk of having an abnormal Pap smear within one year was significantly elevated for women with multiple HPV types at study entry (adjusted odds ratio [aOR] = 6.0; 95% CI: 2.3-15.7) and with a subset of HR HPV types (aOR = 4.2; 95% CI: 1.6-11.2). Detection of multiple concurrent HPV infections may be a useful marker to identify women at risk of developing precancerous lesions in populations of high HPV prevalence.

Sialidase activity in aerobic vaginitis is equal to levels during bacterial vaginosis.

OBJECTIVE: To evaluate levels of proinflammatory cytokines and sialidase activity in aerobic vaginitis (AV) in relation to normal vaginal flora and bacterial vaginosis (BV). STUDY DESIGN: In this cross-sectional study, a total of 682 consecutive non-pregnant women attending the gynecology service were assessed and 408 women were included. Vaginal rinsing samples were collected from 223 women with microscopic finding of BV (n=98), aerobic vaginitis (n=25) and normal flora (n=100). Samples were tested for interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, and sialidase activity. RESULTS: Compared to women with normal flora, vaginal levels of IL-1ß were highly increased in both BV and AV (p<0.0001). Significantly higher vaginal IL-6 was detected in AV (p<0.0001) but not in BV, in relation to normal flora. Women with AV also presented increased IL-8 levels (p<0.001), while those with BV presented levels similar to normal flora. Sialidase was increased in BV and AV compared with the normal group (p<0.0001) but no difference in sialidase activity was observed between BV and AV. CONCLUSION: A more intense inflammatory host response occurs for AV than for BV when compared with normal flora. Furthermore, the increased sialidase activity in AV and BV indicates that both abnormal vaginal flora types can be harmful to the maintenance of a healthy vaginal environment.

Acceptance of self-testing for increased vaginal pH in different subsets of Ugandan women.

We assessed the acceptance of self-testing for vaginal pH in 344 Ugandan women in different clinical settings. Women tested themselves by insertion of a gloved finger into the vagina to test vaginal pH and provide a smear on a glass slide. None of the tested women found the test very difficult: 8% found it somewhat difficult, 16% rather easy and 76% very easy to do. Of the 20% who found it difficult to read the test result, more women were attending a family planning clinic or had a higher diploma (P = 0.001). Pregnant women were least likely to understand of the meaning of the test, while those visiting family planning clinics had the opposite experience. HIV-infected women were most motivated to accept: 95% would be happy to use the test more often if requested, and another 3.5% felt they might be better motivated to do repeat testing after extra explanation. Self-sampling of vaginal pH is well accepted by Ugandan women. Our new method also allows diagnostic work-up by formal microscopy. Before commencing large-scale population screening, unexpected reactions of different subpopulations should be taken into account.

European (IUSTI/WHO) guideline on the management of vaginal discharge, 2011.

Three common infections are associated with vaginal discharge: bacterial vaginosis, trichomoniasis and candidiasis, of which trichomoniasis is a sexually transmitted infection (STI). This guideline covers the presentation and clinical findings of these infections and outlines the differential diagnoses. Recommendations for investigation and management based on currently available evidence are made, including the management of persistent and recurrent infections.

The effect of antifungal treatment on the vaginal flora of women with vulvo-vaginal yeast infection with or without bacterial vaginosis.

Antibacterial therapy may enhance the risk of symptomatic vulvo-vaginal candidosis in susceptible women. We addressed the question whether oral antifungal treatment for vulvo-vaginal candidosis also influences the bacterial vaginal microflora. One hundred and forty-two patients with a culture-proven acute episode of recurrent vulvo-vaginal candidosis (RVC) were treated with fuconazole according to the ReCiDiF regimen (induction dose of 600 mg orally per week followed by 200 mg per week) or with a single dose of 200 mg pramiconazole, a new potent oral triazole. At inclusion, 1 week and 1 month after the end of antifungal treatment, the bacterial microflora was assessed by microscopy of vaginal fluid to detect lactobacillary grades and bacterial vaginosis (BV). The presence of BV was studied in these patients with vulvo-vaginal candidosis after treatment with antifungal medication. At the start of oral antifungal treatment, 6.3% of women with Candida were co-infected with BV. Of the BV-negative women, 10 out of 133 (8%) developed BV after 1 week and after 1 month 8 of them (7%) were still BV-positive. Although no patients received antibacterial treatment at any moment of the study, 6 out of 9 (66%) of the women with Candida and BV at inclusion no longer had BV 1 week after antifungal treatment and 6 out of 7 (86%) lacked BV after 1 month. Treatment with antifungals may have a beneficial effect on women with concurrent BV, but does not prevent BV from occurring in BV-negative women with Candida vaginitis.

Effect of lyophilized lactobacilli and 0.03 mg estriol (Gynoflor®) on vaginitis and vaginosis with disrupted vaginal microflora: a multicenter, randomized, single-blind, active-controlled pilot study.

OBJECTIVES: To evaluate the efficacy of lyophilized lactobacilli in combination with 0.03 mg estriol when compared to metronidazole in the treatment of bacterial vaginal infections. SETTING: Multicenter, randomized, single-blind, active-controlled pilot study in 3 independent gynecological practices in Belgium. METHODS: Forty-six, 18- to 50-year-old premenopausal women with a disrupted vaginal flora due to a bacterial vaginal infection (bacterial vaginosis, aerobic vaginitis) were included, provided that fresh phase-contrast microscopy of the vaginal fluid showed lactobacillary flora grade 2B or 3. Patients were given a blinded box with either 12 vaginal tablets of Gynoflor® (study medication) or 6 vaginal suppositories containing 500 mg metronidazole (control medication). Eight efficacy variables were studied to assess the status of the vaginal flora at entry, 3-7 days (control 1), 4-6 (control 2) weeks and 4 months after the end of therapy. RESULTS: At control 1, the combined variables equally improved in the lactobacilli group as in the metronidazole group. At control 2, the lactobacillus preparation showed slightly inferior results when compared to metronidazole. At 4 months, this analysis could not be performed due to low numbers, but analysis of recurrence rate and extra medication needed was not different between both groups. CONCLUSION: Lyophilized lactobacilli in combination with low-dose estriol are equivalent to metronidazole in the short-term treatment of bacterial vaginal infections, but have less effect after 1 month. Further studies are required to evaluate the long-term efficacy of lactobacilli when applied repeatedly.