Bacterial vaginosis in a subfertile population undergoing fertility treatments: a prospective cohort study.

PURPOSE: This study investigates the role of bacterial vaginosis (BV) on pregnancy rates during various fertility treatments. BV is known to influence several obstetric outcomes, such as preterm delivery and endometritis. Only few studies investigated the effect of BV in subfertile women, and studies found a negative effect on fecundity especially in the in vitro fertilisation population. METHODS: Observational prospective study, 76 couples attending a fertility clinic in the Netherlands between July 2019 and June 2022, undergoing a total of 133 attempts of intra uterine insemination, in vitro fertilization or intra cytoplasmatic sperm injection. Vaginal samples taken at oocyte retrieval or insemination were analysed on qPCR BV and 16S rRNA gene microbiota analysis of V1-V2 region. Logistic regression with a Generalized Estimated Equations analysis was used to account for multiple observations per couples. RESULTS: A total of 26% of the 133 samples tested positive for BV. No significant differences were observed in ongoing pregnancy or live birth rates based on BV status (OR 0.50 (0.16-1.59), aOR 0.32 (0.09-1.23)) or microbiome community state type. There was a tendency of more miscarriages based on positive BV status (OR 4.22 (1.10-16.21), aOR 4.28 (0.65-28.11)) or community state type group III and IV. On baseline qPCR positive participants had significantly higher body mass index and smoked more often. Odds ratios were adjusted for smoking status, body mass index, and socioeconomic status. CONCLUSION: Bacterial vaginosis does not significantly impact ongoing pregnancy rates but could affect miscarriage rates.

Changes of the bacterial composition in duodenal fluid from patients with liver cirrhosis and molecular bacterascites.

Small intestinal bacterial overgrowth and compositional changes of intestinal microbiota are pathomechanistic factors in liver cirrhosis leading to bacterial translocation and infectious complications. We analyzed the quantity and composition of duodenal bacterial DNA (bactDNA) in relation to bactDNA in blood and ascites of patients with liver cirrhosis. Duodenal fluid and corresponding blood and ascites samples from 103 patients with liver cirrhosis were collected. Non-liver disease patients (n = 22) served as controls. BactDNA was quantified by 16S-rRNA gene-based PCR. T-RFLP and 16S-rRNA amplicon sequencing were used to analyze bacterial composition. Duodenal bacterial diversity in cirrhosis was distinct to controls showing significantly higher abundances of Streptococcus, Enterococcus and Veillonella. Patients with bactDNA positive ascites revealed reduced spectrum of core microbiota with Streptococcus as key player of duodenal community and higher prevalence of Granulicatella proving presence of cirrhosis related intestinal dysbiosis. Regarding duodenal fluid bactDNA quantification, no significant differences were found between patients with cirrhosis and controls. Additionally, percentage of subjects with detectable bactDNA in blood did not differ between patients and controls. This study evaluated the diversity of bacterial DNA in different body specimens with potential implications on understanding how intestinal bacterial translocation may affect infectious complications in cirrhosis.

Topical antimicrobial peptide omiganan recovers cutaneous dysbiosis but does not improve clinical symptoms in patients with mild to moderate atopic dermatitis in a phase 2 randomized controlled trial.

BACKGROUND: Dysbiosis and colonization with Staphylococcus aureus is considered to play an important role in the pathogenesis of atopic dermatitis (AD). Recovering this dysbiosis may improve AD symptoms. Omiganan is a synthetic indolicidin analogue antimicrobial peptide with activity against S aureus and could be a viable new treatment option for AD. OBJECTIVE: To explore the tolerability, clinical efficacy, and pharmacodynamics of omiganan in mild to moderate AD. METHODS: Eighty patients were randomized to omiganan 1%, 1.75%, or 2.5% or vehicle twice daily for 28 days on all lesions. Weekly visits included clinical scores and microbiological and pharmacodynamic assessments of 1 target lesion. RESULTS: In all omiganan treatment groups, dysbiosis was recovered by reducing Staphylococcus species abundance and increasing diversity. A reduction of cultured S aureus was observed in all omiganan treatment groups, with a significant reduction for omiganan 2.5% compared to vehicle (-93.5%; 95% CI, -99.2 to -28.5%; P = .02). No significant clinical improvement was observed. CONCLUSION: Topical administration of omiganan twice daily for up to 28 days in patients with mild to moderate AD led to a recovery of dysbiosis but without clinical improvement. Therefore, a monotreatment that selectively targets the microbiome does not appear to be a successful treatment strategy in mild to moderate AD.

Developing an algorithm for the diagnosis of abnormal vaginal discharge in a dutch clinical setting: a pilot study.

Abnormal vaginal discharge may be caused by bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis and/or aerobic vaginitis. For the development of a diagnostic algorithm, tree-based classification analysis was performed on symptoms, signs and bedside test results of 56 patients, and laboratory tests (culture, Nugent score, qPCRs) were compared. Amplicon sequencing of the 16S rRNA gene was used as reference test for bacterial vaginosis and aerobic vaginitis, culture for vulvovaginal candidiasis and qPCR for trichomoniasis. For bacterial vaginosis, the best diagnostic algorithm was to screen at the bedside with a pH and odour test and if positive, to confirm by qPCR (sensitivity 94%; specificity 97%) rather than Nugent score (sensitivity of 59%; specificity 97%; P = 0.031). The analysis for the other infections was less conclusive due to the low number of patients with these infections. For bacterial vaginosis, the developed algorithm is sensitive, specific, and reduces the need for laboratory tests in 50% of the patients.

Balanopreputial sac and urine microbiota in patients with male genital lichen sclerosus.

BACKGROUND: Male genital lichen sclerosus (MGLSc) is a chronic inflammatory scarring dermatosis associated with penile carcinoma. The prepuce is pivotal in its etiology. Other proposed etiological factors are the subject of dispute and include occluded urinary exposure, autoimmunity, immunodysregulation, and infectious agents. OBJECTIVE: To determine whether the bacterial microbiota of the balanopreputial sac and urine are associated with MGLSc. SUBJECTS AND METHODS: Twenty uncircumcised patients with MGLSc and 20 healthy uncircumcised males were enrolled in a prospective case-control study. Balanopreputial swabs and urine specimens were subjected to 16S rRNA gene amplicon sequencing. RESULTS: Microbiota analysis indicated differences between the groups. In the balanopreputial sac, the median relative abundance of Finegoldia spp. was lower (9% [range 0-60%]) in MGLSc patients than in controls (28% [range 0-62%]). Conversely, the median relative abundance of Fusobacterium spp. was higher in MGLSc patients (4% [range 0-41%]) than in controls (0% [range 0-28%]). In the urine, the median relative abundance of Finegoldia spp. was comparable between groups, whereas that of Fusobacterium spp. was higher in MGLSc patients (0% [range 0-18%] vs. 0% [range 0-5%]). There was a strong association between the microbiota composition of the balanopreputial sac and urine in MGLSc. CONCLUSION: Dysbiosis could be involved in the etiopathogenesis of MGLSc. Further studies are required to confirm the association suggested herein and to determine its nature.

The vaginal microbiota in the course of bacterial vaginosis treatment.

Bacterial vaginosis (BV) is perceived as a condition of disrupted vaginal microbiota, but remains of unknown aetiology. In this study, vaginal microbiota composition was determined in twenty-one women with BV, before and after treatment with metronidazole or clindamycin. Microbiota composition varied greatly between women and defining a (un)healthy vaginal microbiota state remains elusive, challenging BV diagnosis and treatment. While relative abundance of Lactobacillus increased after antibiotic treatment in two-third of women, its abundance was not associated with treatment outcome. Instead, remaining complaints of abnormal vaginal discharge were more common after metronidazole treatment and associated with increased relative abundance of Ureaplasma.

Nasal microbiota dominated by Moraxella spp. is associated with respiratory health in the elderly population: a case control study.

BACKGROUND: The elderly (≥65 years) are one of the populations most at risk for respiratory tract infections (RTIs). The aim of this study was to determine whether nasal and/or oropharyngeal microbiota profiles are associated with age and RTIs. METHODS: Nasal and oropharyngeal swabs of 152 controls and 152 patients with an RTI were included. The latter group consisted of 72 patients with an upper respiratory tract infection (URTI) and 80 with a lower respiratory tract infection (LRTI). Both nasal and oropharyngeal swabs were subjected to microbiota profiling using amplicon sequencing of the 16S rRNA gene. Moraxella species were determined using quantitative real-time PCR and culture. RESULTS: Based on the microbiota profiles of the controls and the patients with an RTI, eight nasal and nine oropharyngeal microbiota clusters were defined. Nasal microbiota dominated by either Moraxella catarrhalis or Moraxella nonliquefaciens was significantly more prevalent in elderly compared to mid-aged adults in the control group (p = 0.002). Dominance by M. catarrhalis/nonliquefaciens was significantly less prevalent in elderly with an LRTI (p = 0.001) compared to controls with similar age. CONCLUSIONS: Nasal microbiota dominated by M. catarrhalis/nonliquefaciens is associated with respiratory health in the elderly population.

Pharmacodynamic Effects of Topical Omiganan in Patients With Mild to Moderate Atopic Dermatitis in a Randomized, Placebo-Controlled, Phase II Trial.

Omiganan is an indolicidin analog with antimicrobial properties that could be beneficial for patients with atopic dermatitis. In this randomized, double-blind, placebo-controlled, phase II trial we explored the efficacy, pharmacodynamics, and safety of topical omiganan once daily in 36 patients with mild to moderate atomic dermatitis. Patients were randomized to apply topical omiganan 1%, omiganan 2.5%, or vehicle gel to one target lesion once daily for 28 consecutive days. Small but significant improvements in local objective SCORing Atopic Dematitis index and morning itch were observed in the omiganan 2.5% group compared with the vehicle gel group (-18.5%; 95% confidence interval, -32.9 to -1.0; P = 0.04; and -8.2; 95% confidence interval, -16.3 to -0.2; P = 0.05, respectively). A shift from lesional to nonlesional skin microbiota was observed in both omiganan treatment groups, in contrast to the vehicle group. Thus, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis, and small but statistically significant improvements in clinical scores were detected. Our findings warrant further exploration in future clinical trials.

Comparison of Amsel criteria, Nugent score, culture and two CE-IVD marked quantitative real-time PCRs with microbiota analysis for the diagnosis of bacterial vaginosis.

Bacterial vaginosis (BV) is a common gynaecological condition. Diagnosis of BV is typically based on Amsel criteria, Nugent score and/or bacterial culture. In this study, these conventional methods and two CE-IVD marked quantitative real-time (q)PCR assays were compared with microbiota analysis for the diagnosis of BV. Eighty women were evaluated for BV during two sequential hospital visits by Amsel criteria, Nugent score, culture, the AmpliSens® Florocenosis/Bacterial vaginosis-FRT PCR kit (InterLabService, Moscow, Russia), and the BD MAX™ Vaginal Panel (BD Diagnostics, MD, USA). Microbiota analysis based on amplicon sequencing of the 16S ribosomal RNA gene was used as reference test. The microbiota profile of 36/115 (31%) included cases was associated with BV. Based on microbiota analysis, the sensitivity of detecting BV was 38.9% for culture, 61.15% for Amsel criteria, 63.9% for Nugent score and the BD MAX assay, and 80.6% for the AmpliSens assay, while the specificity of all methods was ≥ 92.4%. Microbiota profiles of the cases with discrepant results between microbiota analysis and the diagnostic methods were variable. All five diagnostic methods missed BV positive cases with a relatively high abundance of the genus Alloscardovia, Bifidobacterium, or Dialister, which were categorised as unspecified dysbiosis by the AmpliSens assay. Compared to Amsel criteria, Nugent score, culture, and the BD MAX assay, the AmpliSens assay was most in agreement with microbiota analysis, indicating that currently, the AmpliSens assay may be the best diagnostic method available to diagnose BV in a routine clinical setting.

Evaluation of a stepwise approach using microbiota analysis, species-specific qPCRs and culture for the diagnosis of lower respiratory tract infections.

In clinical practice, the diagnosis of lower respiratory tract infections (LRTIs) is based on culture. The aim of this study was to evaluate whether a stepwise approach using microbiota analysis, species-specific quantitative real-time (q)PCRs and culture has the potential to be a more accurate and efficient diagnostic approach than culture alone. Sixty-two sputa obtained in a routine clinical setting from patients with a suspected LRTI were included. All sputa were analysed by culture, microbiota analysis based on the 16S ribosomal RNA gene and multiple species-specific qPCRs. Microbiota and culture data were compared to investigate whether cut-off values for microbiota analysis could be determined. For microbiota analysis, a relative abundance of 25% was identified as the cut-off value for the detection of both genera Streptococcus and Haemophilus. Microbiota analysis combined with species-specific qPCRs resulted in a significant increase in the number of positive sputa (73% vs 58%; p = 0.003) as well as in the number of identified pathogens (51 vs 37; p = 0.049) compared to culture. A stepwise approach using microbiota analysis, species-specific qPCRs and culture has the potential to be used in clinical settings for the diagnosis of LRTIs in the near future.