Lactobacillus probiotic for prevention of recurrent UTI

乳酸菌益生菌预防复发性尿路感染

• 批准号: 8332134
• 负责人: Ann E Stapleton
• 金额: $ 61.01万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8332134
• 关键词: Acute; Adverse effects; Adverse reactions; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Bacterial Vaginosis; Bacteriuria; Biological Assay; Client satisfaction; Clinical; Clinical Data; Controlled Study; Cost Analysis; DNA; Development; Double-Blind Method; Effectiveness; Enrollment; Environment; Epithelial Cells; Escherichia coli; Evaluation; Fostering; Funding; Future; Genome; Health; Health Care Costs; High Risk Woman; Hydrogen Peroxide; Incidence; Infection; Inflammatory; Intervention; Intravaginal Administration; Knowledge; Lactic acid; Lactobacillus; Letters; Measures; Methods; Morbidity - disease rate; Outcome; Outpatients; Pharmaceutical Preparations; Phase; Placebos; Population; Premenopause; Prevention; Prevention approach; Prevention strategy; Preventive; Probiotics; Prophylactic treatment; Public Health; Randomized; Recording of previous events; Recruitment Activity; Recurrence; Risk; Risk Factors; Safety; Specimen; Students; Technology; Time; Urinary tract infection; Urine; Uropathogen; Vagina; Visit; Woman; antimicrobial; arm; base; community-acquired UTI; cost; cytokine; design; double-blind placebo controlled trial; follow-up; insight; lost work time; microbial host; microbicide; microbiome; novel; novel strategies; phase 3 study; placebo controlled study; prevent; rRNA Genes; tool; trial comparing; two-arm study; vaginal fluid; vaginal lactobacilli; young woman

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.

UTI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保健费用。此外，抗生素耐药性的增加，即使是在社区获得性UTI中，也使治疗成为问题。因此，迫切需要新的非抗生素预防策略。在机理水平上有强有力证据的一种这样的方法是使用产生H2O2的益生菌来恢复正常的阴道植物群。如果能有效降低E.大肠杆菌定植和复发性UTI（鲁蒂），该策略将降低与UTI相关的成本和发病率，包括抗生素耐药性的发展。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测定（qPCR），现在可用于准确和定量地跟踪益生菌的定植以及益生菌诱导的阴道植物群的改变和这些结果与鲁蒂的关系。因此，我们提出一个随机，双盲，安慰剂对照研究，以评估是否阴道内L。卷曲酵母益生菌能恢复正常植物群，消除大肠杆菌。大肠杆菌阴道定植，降低鲁蒂的发生率。我们建议使用一种特定的L. crispatus已经被我们和其他人广泛研究，并且已知其贪婪地粘附于阴道上皮细胞，排除E.大肠杆菌定植，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。在学生健康中心就诊的200名妇女将被招募、登记、随机化并随访4个月。用于培养的尿液标本和用于种属特异性qPCR的阴道标本。crispatus，L. jensenii湖gasseri和L.将在研究开始时、两周时和此后每月收集Iners。还将在阴道液中测量选定的细胞因子。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，并将为鲁蒂中涉及的宿主和微生物机制提供新的见解。