Lactobacillus probiotic for prevention of recurrent UTI

描述：尿路感染是年轻女性中非常常见的门诊问题，导致相当大的发病率和医疗费用。此外，抗生素耐药性的增加，甚至在社区获得性尿路感染中也是如此，这使得治疗成为问题。因此，迫切需要新的非抗菌素预防策略。其中一种在机制层面上有强有力证据的方法是使用一种产生过氧化氢的乳杆菌益生菌来恢复正常的阴道菌群。如果在减少大肠埃希氏菌定植和复发尿路感染(RUTI)方面有效，这一策略将降低与尿路感染相关的成本和发病率，包括发展抗菌素耐药性。需要使用精心挑选和预先测试的益生菌进行良好的对照研究，以评估这种方法是否具有预防价值。此外，新的工具，如定量16S rRNA基因聚合酶链式反应分析(Q-PCR)现在可用于准确和定量地跟踪益生菌的定植以及益生菌引起的阴道菌群变化以及这些结果与RUTI的关系。因此，我们提出了一项随机、双盲、安慰剂对照研究，以评估阴道内使用皱纹乳杆菌益生菌能否恢复正常菌群、消除大肠杆菌阴道定植并降低RUTI的发生率。我们建议使用一种特定的皱纹乳杆菌菌株，这种菌株已经由我们和其他人进行了广泛的研究，众所周知，它可以热衷于附着在阴道上皮细胞上，排除大肠杆菌的定植，产生过氧化氢和其他杀菌化合物，降低阴道pH值，并在服用益生菌后持续很长时间。在学生健康中心看到的200名女性将被招募、登记、随机并跟踪调查4个月。用于培养的尿样和阴道标本将在研究开始时收集，两周后每月收集，用于对皱纹夜蛾、简氏乳杆菌、加色乳杆菌和乳杆菌进行种特异性定量聚合酶链式反应。选定的细胞因子也将在阴道液中进行检测。这项试验将评估阴道益生菌在建立定植和预防尿路感染方面的有效性，并将为RUTI涉及的宿主和微生物机制提供新的见解。 与公共卫生相关：尿路感染是一种非常常见的感染，会导致相当大的发病率、医疗费用、工作时间损失和抗生素使用，这会促进抗生素耐药性的产生。因此，迫切需要预防尿路感染的新的非抗菌手段。我们建议进一步评估阴道给药的皱纹乳杆菌益生菌，它有相当多的机制和临床数据表明潜在的有效性。

DESCRIPTION: UTI is an exceedingly common outpatient problem among young women, resulting in considerable morbidity and health care costs. In addition, increasing antibiotic resistance, even among community-acquired UTIs, is making treatment problematic. Thus, novel non-antimicrobial prevention strategies are urgently needed. One such approach for which there is strong evidence at the mechanistic level is use of an H2O2 producing lactobacillus probiotic to restore normal vaginal flora. If effective in reducing E. coli colonization and recurrent UTI (rUTI) this strategy would reduce the costs and morbidity associated with UTI, including the development of antimicrobial resistance. Well controlled studies using a carefully selected and pretested probiotic are needed to assess whether this approach is of preventive value. Additionally, new tools, such as quantitative 16S rRNA gene PCR assays (q PCR) are now available to accurately and quantitatively follow colonization with the probiotic as well as the alterations in the vaginal flora induced by the probiotic and the relationship of these outcomes to rUTI. We thus propose a randomized, double blind, placebo controlled study to assess whether an intravaginal L. crispatus probiotic can restore the normal flora, eliminate E. coli vaginal colonization and reduce the incidence of rUTI. We propose using a specific strain of L. crispatus that has been extensively studied by ourselves and others and is known to avidly adhere to vaginal epithelial cells, exclude E. coli colonization, produce H2O2 and other microbicidal compounds, reduce vaginal pH and persist for long periods after being given as a probiotic. Two-hundred women seen at the student health center will be recruited, enrolled, randomized and followed for 4 months. Urine specimens for culture and vaginal specimens for species specific qPCR for L. crispatus, L. jensenii, L. gasseri, and L. iners will be collected at study entry, at two weeks and monthly thereafter. Selected cytokines will be measured in vaginal fluid as well. The trial will assess the efficacy of the vaginal probiotic in terms of both establishing colonization and preventing UTI and will also provide new insights into both host and microbial mechanisms involved in rUTI. PUBLIC HEALTH RELEVANCE: UTIs are very common infections that result in considerable morbidity, health care costs, time lost from work and antibiotic use, which fosters antibiotic resistance. Novel non-antimicrobial means of preventing UTI are thus urgently needed. We propose further evaluation of a vaginally administered Lactobacillus crispatus probiotic, which has considerable mechanistic and clinical data suggesting potential effectiveness.