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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK088830-04
Application #
8706851
Study Section
Urologic and Kidney Development and Genitourinary Diseases Study Section (UKGD)
Program Officer
Bavendam, Tamara G
Project Start
2011-09-15
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
4
Fiscal Year
2014
Total Cost
$610,127
Indirect Cost
$219,020
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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