H2O2-PRODUCING LACTOBACILLI AND POSTMENOPAUSAL UTI

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DESCRIPTION (adapted from the application) Urinary tract infections affect over 7 million women per year, and the incidence of UTI increases with advancing age. Although marked strides have been made in our understanding of the pathogenesis of UTI in young adult women, the pathogenesis and epidemiology of UTI among postmenopausal women remain poorly understood, especially among the non-institutionalized segment of the population. Vaginal colonization with E. coli has been shown to be an important event preceding UTI, and it is highly prevalent in postmenopausal women. In vitro studies suggest that the predominant constituents of normal vaginal flora, H202-producing lactobacilli, are inhibitory to E. coli. Our recent data demonstrate that there is, indeed, an inverse relationship between the presence of H202-producing lactobacilli and E. coli vaginal colonization in premenopausal women with recurrent UTI. However, the prevalence of H202-producing lactobacilli, and their relationship to vaginal E. coli colonization and to the incidence of UTI among postmenopausal women has not been characterized. A prospective evaluation of the incidence of and risk factors for UTI in 1000 community-dwelling postmenopausal women (DK43134, Stephan D. Fin, MD, MPH) has been initiated at the Group Health Cooperative of Puget Sound, a population-based HMO in western Washington. Based on our findings in premenopausal women, we are proposing additional studies which will enable us to (1) establish the prevalence of vaginal lactobacilli, characterized by H202 status and by species, in postmenopausal women; (2) examine the relationship between H202-producing lactobacilli and E. coli vaginal colonization; (3) relate this information to the incidence of UTI and asymptomatic bacteriuria in postmenopausal women while accounting for exposures such as estrogen use, diabetes, and antimicrobial use; (4) assess the prevalence of urovirulence genes in E. coli strains causing cystitis in postmenopausal women; and (5) assess the feasibility of using a lactobacillus probiotic to prevent UTI in postmenopausal women. These additional studies will entail a combination of epidemiological, biostatistical, and laboratory methods which, in combination with structured didactic and classroom instruction, will provide an excellent training experience for the development of the Candidate into a successful, independent, clinical investigator.