Community-onset urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in women of diverse backgrounds

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PROJECT SUMMARY This is an application for a Career Development Award for Dr. Eva Raphael, a clinical research fellow and future Assistant Professor at the University of California, San Francisco. Her career goal is to be a family medicine-trained clinician-researcher improving prevention and outcomes for community-onset antimicrobial resistant infections by combining epidemiological methods to identify novel risk factors that can be intervened upon. This award will provide her with the training and research experience to: (1) examine demographic and neighborhood-level risk factors for community-onset urinary tract infections (UTI) caused by ESBL-producing Escherichia coli (ESBL-UTI) among women; (2) identify complications for community-onset ESBL-UTI and associated risk factors; and (3) investigate whether the temporal and geographic trends in prevalence of community-onset ESBL-UTI correlate with trends in prevalence of predominant E. coli genotypes. To facilitate successful completion of these activities, Dr. Raphael has assembled an ideal mentoring team comprised of two co-primary mentors, Dr. Maria Glymour, an expert in social epidemiology methods and health inequities research, and Dr. Henry Chambers, an expert in clinical antimicrobial resistance research, and a co-mentor, Dr. Alison Huang, an expert in genitourinary health in older women and patient-reported outcomes. In addition, Dr. Raphael will have 2 advisors: Dr. Salma Shariff-Marco, an expert in spatial epidemiology and neighborhood effect on health outcomes, and Dr. Sara Tartof, an infectious disease epidemiologist who focuses on antimicrobial resistance. The prevalence of antimicrobial resistant infections is increasing worldwide, both in healthcare and community settings. While antibiotic use is a major driver for selection of antimicrobial resistant organisms, novel risk factors are beginning to be identified for transmission of such organisms, especially in diverse populations. Moreover, new evidence suggests antimicrobial resistant infections, particularly UTI, may occur as community outbreaks. Therefore, it is essential to further examine risk factors other than antibiotic use for UTI caused by antimicrobial-resistant E. coli, in particular ESBL-UTI, and whether they occur as outbreaks in diverse communities. Dr. Raphael will build on findings from prior work showing that prevalence of community- onset ESBL-UTI has increased in a San Francisco public safety-net healthcare system and differed by race/ethnicity and age. Dr. Raphael will employ causal inference methods to identify novel individual and neighborhood risk factors for ESBL-UTI compared to both non-ESBL antimicrobial resistant and susceptible UTI and their complications (Aims 1 and 2). Through spatial analyses, geographic clusters of predominant E. coli genotypes causing UTI, particularly ESBL-UTI, will be identified and compared to geographic distribution of ESBL-UTI phenotypes (Aim 3). This work will be the basis of an R01 proposal for a longitudinal study identifying multilevel risk factors and incidence of UTI recurrence and complications in a cohort of community- dwelling women diagnosed with UTI. Through a focused program of mentored training and coursework, the candidate will gain skills in: (1) social epidemiology methods; (2) spatial epidemiology; and (3) patient-reported outcomes research methods as they apply to community-onset infections. These skills will facilitate Dr. Raphael's transition to independence by uniquely positioning her to address multilevel factors to improve community-onset infections outcomes in diverse populations.