Lactobacillus probiotic for prevention of recurrent UTI

描述：尿路感染是一个非常常见的门诊问题，在年轻女性，导致相当大的发病率和医疗费用。此外，即使在社区获得性尿路感染中，抗生素耐药性也在增加，这给治疗带来了问题。因此，迫切需要新的非抗菌素预防策略。在机制水平上有强有力证据的一种这样的方法是使用产生H2O2的益生乳杆菌来恢复正常的阴道菌群。如果有效减少大肠杆菌定植和复发性尿路感染（rUTI），该策略将降低与尿路感染相关的成本和发病率，包括抗菌素耐药性的发展。需要使用精心选择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PCR (q PCR)，现在可以准确和定量地跟踪益生菌的定植，以及益生菌诱导的阴道菌群的变化，以及这些结果与rUTI的关系。因此，我们提出了一项随机、双盲、安慰剂对照的研究，以评估阴道内crispatus益生菌是否能恢复正常菌群，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crispatus菌株，这种菌株已经被我们和其他人广泛研究过，已知它能强烈地附着在阴道上皮细胞上，排除大肠杆菌的定植，产生H2O2和其他杀微生物化合物，降低阴道pH值，并在作为益生菌给予后持续很长时间。在学生健康中心看到的200名女性将被招募、登记、随机化并随访4个月。尿液样本用于培养，阴道样本用于crispatus、L. jensenii、L. gasseri和L. iners的物种特异性qPCR，将在研究开始时收集，之后每两周和每月收集一次。选定的细胞因子也将在阴道液中测量。该试验将评估阴道益生菌在建立定植和预防UTI方面的功效，并将为涉及rUTI的宿主和微生物机制提供新的见解。

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.