Lactobacilli, principally the strains that are hydrogen peroxide (H 2 O 2 ) producing, may have a protective effect against vaginal colonization by pathogenic species such as those that cause bacterial vaginosis. Previous reports have also suggested that H 2 O 2 -producing lactobacilli in the vagina may protect pregnant women against ascending infection of the chorioamniotic membranes and uterine cavity. We report the identification and H 2 O 2 production of lactobacilli isolated from vaginal swabs collected at 20 weeks' gestation from a population of pregnant women at high risk of preterm birth. We also report the correlation between identification and H 2 O 2 production in relation to the outcomes of chorioamnionitis and preterm birth. Lactobacilli were identified by partial 16S rRNA gene sequencing. H 2 O 2 production by isolates was determined by a semiquantitative method. The most commonly isolated species were L. crispatus, L. gasseri, L. vaginalis and L. jensenii. Amounts of H 2 O 2 produced by lactobacilli varied widely. The presence of lactobacilli producing high levels of H 2 O 2 in the vagina of this population of pregnant women was associated with a reduced risk of bacterial vaginosis at 20 weeks' gestation and subsequent chorioamnionitis. L. jensenii and L. vaginalis produced the highest levels of H 2 O 2 . We postulate that H 2 O 2 -producing lactobacilli are able to reduce the incidence of ascending infections of the uterus and the subsequent production of proinflammatory molecules which are important in the pathogenesis of chorioamnionitis and preterm birth.The adult human vagina is a complex ecosystem containing an abundance of microorganisms. In women of childbearing age this system is dominated by Lactobacillus spp., a genus of gram-positive, nonmotile rod-like bacteria, a defining characteristic of which is the ability to grow in acid media and tolerate acid conditions (pH Ͻ 4.5); lactobacilli also ferment carbohydrates to produce lactic acid. In bacterial vaginosis (BV) the balance of flora is changed with reduced numbers of lactobacilli and an increase in numbers of other facultative and anaerobic species such as anaerobic cocci Prevotella spp., Gardnerella vaginalis, and Mobiluncus spp. BV is associated with a number of poor health outcomes, including preterm birth (31). Lactobacilli, principally the strains that are H 2 O 2 producing, may have a protective effect against vaginal colonization by pathogenic species such as those that cause BV (16) and possibly human immunodeficiency virus and gonorrhoea (26). Previous reports have also suggested that H 2 O 2 -producing lactobacilli in the vagina may protect pregnant women against ascending infection of the chorioamniotic membranes and uterine cavity (12, 18). There have been few studies in which lactobacilli have been identified to species level and in which H 2 O 2 production in pregnant women has been determined. We report the identification and H 2 O 2 production of lactobacilli isolated from vaginal swabs collected at 20 weeks' gestatio...

BackgroundNecrotising enterocolitis (NEC) and late-onset sepsis remain important causes of death and morbidity in preterm babies. Probiotic administration might strengthen intestinal barrier function and provide protection; this is supported by published meta-analyses, but there is a lack of large well-designed trials.ObjectiveTo test the use of the probioticBifidobacterium brevestrain BBG-001 to prevent NEC, late-onset sepsis and death in preterm babies while monitoring probiotic colonisation of participants.DesignDouble-blind, randomised, placebo-controlled trial.SettingRecruitment was carried out in 24 hospitals, and the randomisation programme used a minimisation algorithm. Parents, clinicians and outcome assessors were blinded to the allocation.ParticipantsBabies born between 23 and 30 weeks’ gestation and randomised within 48 hours of birth. Exclusions included life-threatening or any gastrointestinal malformation detected within 48 hours of birth and no realistic chance of survival.InterventionsActive intervention: 1 ml ofB. breveBBG-001 in one-eighth-strength infant formula Neocate®(Nutricia Ltd, Trowbridge, UK), (6.7 × 107to 6.7 × 109colony-forming units) per dose administered enterally. Placebo: 1 ml of one-eighth-strength infant formula Neocate. Started as soon as practicable and continued daily until 36 weeks’ postmenstrual age.Main outcome measuresPrimary outcomes were an episode of bloodstream infection, with any organism other than a skin commensal, in any baby between 72 hours and 46 weeks’ postmenstrual age; an episode of NEC Bell stage ≥ 2 in any baby; and death before discharge from hospital. Secondary outcomes included stool colonisation withB. breve.ResultsIn total, 654 babies were allocated to receive probiotic and 661 to receive placebo over 37 months from July 2010. Five babies were withdrawn; 650 babies from the probiotic group and 660 from the placebo group were included in the primary analysis. Baseline characteristics were well balanced. There was no evidence of benefit for the primary outcomes {sepsis: 11.2% vs. 11.7% [adjusted relative risk (RR) 0.97, 95% confidence interval (CI) 0.73 to 1.29]; NEC Bell stage ≥ 2: 9.4% vs. 10.0% [adjusted RR 0.93, 95% CI 0.68 to 1.27]; and death: 8.3% vs. 8.5% [adjusted RR 0.93, 95% CI 0.67 to 1.30]}.B. brevecolonisation status was available for 1186 (94%) survivors at 2 weeks’ postnatal age, of whom 724 (61%) were positive: 85% of the probiotic group and 37% of the placebo group. There were no differences for subgroup analyses by minimisation criteria and by stool colonisation withB. breveat 2 weeks. No harms associated with the interventions were reported.LimitationsCross-colonisation of the placebo arm could have reduced statistical power and confounded results; analyses suggest that this did not happen.ConclusionsThis is the largest trial to date of a probiotic intervention. It shows no evidence of benefit and does not support routine use of probiotics for preterm infants.Future work recommendationsThe increasing understanding of the pathogenesis of NEC and sepsis will inform the choice of probiotics for testing and better define the target population. Future Phase III trials should incorporate monitoring of the quality and viability of the intervention and colonisation rates of participants; cluster design should be considered.Trial registrationCurrent Controlled Trials ISRCTN05511098 and EudraCT 2006-003445-17.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 66. See the NIHR Journals Library website for further project information.

Azithromycin is an azalide antibiotic with excellent in vitro activity against a wide variety of oral bacteria. It has a long half-life, good tissue penetration and is preferentially taken up by phagocytes. We investigated the microbiological efficacy of azithromycin as an adjunct to the non-surgical treatment of adult chronic periodontitis; its clinical efficacy is dealt with in a separate paper. 46 patients were treated in a double-blind placebo controlled trial. Microbiological assessment of the same periodontal pocket (initially > 6 mm) was made at weeks 0, 2, 3, 6, 10 and 22. Either azithromycin 500 mg 1 x daily for 3 days or placebo was given at week 2. Particular attention was paid to the numbers of black pigmented anaerobes and spirochaetes present since these are the most commonly implicated pathogens in periodontal disease. Pigmented anaerobes were significantly reduced at weeks 3 and 6 in patients who received azithromycin compared to placebo and remained lower, although not significantly so, throughout the study. Counts of spirochaetes were significantly reduced throughout the study in patients who received azithromycin compared to placebo. Our microbiological study suggests that azithromycin may be useful as an adjunct in the treatment of periodontal disease.

Objective To determine the effects on the vaginal microbiota of an oral probiotic preparation administered from early pregnancy.Design Randomised, double blind, placebo-controlled trial.Setting Four maternity units in the UK.Population Women aged 16 years or older recruited at 9-14 weeks' gestation.Methods Participants were randomly allocated to receive oral capsules of probiotic containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each at 2.5 9 10 9 colony-forming units (CFUs) or placebo once daily from recruitment until the end of pregnancy.Main outcome measure Rates of bacterial vaginosis (BV, defined as Nugent score ≥7) at 18-20 weeks' gestation compared by logistic regression adjusted for possible confounders. ResultsThe primary analysis included 78% (238/304) of participants who initially consented (probiotic group 123, placebo group 115). Of these participants, 95% (227/238) reported an intake of 93% or more of the required number of capsules. The rates of BV did not differ between groups at 18-20 weeks' gestation (15% (19/123) in the probiotic group vs. 9% (10/115) in the placebo group, adjusted odds ratio 1.82, 95% confidence interval 0.64-5.19). There were also no differences between the groups in the proportion of women colonised with the probiotic strains, Escherichia coli, group B streptococci or other vaginal microbiota. There were no differences in the alpha diversity or composition of the bacterial communities between or within the probiotic and placebo groups at 9-14 and 18-20 weeks' gestation.Conclusions Oral probiotics taken from early pregnancy did not modify the vaginal microbiota.