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

项目摘要 这是伊娃拉斐尔博士职业发展奖的申请，她是一名临床研究员， 未来的助理教授在加州大学，旧金山弗朗西斯科。她的职业目标是成家 受过医学培训的临床医生-研究人员改善了社区发病抗菌药物的预防和结果 通过结合流行病学方法确定可干预的新风险因素， 上。该奖项将为她提供培训和研究经验，以：（1）研究人口统计学和 产ESBL细菌引起的社区发病性尿路感染（UTI）的社区水平危险因素 大肠埃希菌（ESBL-UTI）在妇女中的分布;（2）确定社区发病ESBL-UTI的并发症， 相关的危险因素;（3）调查是否流行的时间和地理趋势， 社区发病的ESBL-UTI与主要大肠杆菌的流行趋势相关。coli基因型。以促进 成功完成这些活动后，Raphael博士组建了一个理想的指导团队， 两名共同的主要导师，玛丽亚·加图尔博士，社会流行病学方法和卫生不平等问题专家 研究，和亨利钱伯斯博士，在临床抗菌素耐药性研究的专家，和共同导师， 博士Alison Huang是老年女性泌尿生殖健康和患者报告结果的专家。此外，本发明还提供了一种方法， 博士拉斐尔将有2名顾问：Salma Shariff-Marco博士，空间流行病学和邻里专家 对健康结果的影响，以及传染病流行病学家Sara Tartof博士，他专注于 抗菌素耐药性 在全球范围内，无论是在医疗保健领域， 社区设置。虽然抗生素的使用是选择抗微生物药物耐药微生物的主要驱动因素， 新的风险因素开始被确定为这种生物体的传播，特别是在不同的环境中。 人口。此外，新的证据表明，抗生素耐药性感染，特别是UTI，可能发生， 社区爆发。因此，有必要进一步检查UTI的风险因素，而不是抗生素的使用 由耐药E.大肠杆菌，特别是ESBL-UTI，以及它们是否在 多样化的社区。拉斐尔博士将建立在先前工作的发现基础上，这些发现表明社区- 在旧金山弗朗西斯科公共安全网医疗保健系统中，ESBL-UTI的发病率增加， 种族/民族和年龄。拉斐尔博士将采用因果推理方法，以确定新的个人和 ESBL-UTI与非ESBL抗生素耐药和敏感的邻居风险因素相比 UTI及其并发症（目标1和2）。通过空间分析，得出了优势种E. 将鉴定引起UTI，特别是ESBL-UTI的大肠杆菌基因型，并与 ESBL-UTI表型（目的3）。这项工作将成为R 01纵向研究提案的基础 在社区队列中确定多水平风险因素和UTI复发和并发症的发生率- 被诊断为UTI的女性。 通过有针对性的指导培训和课程计划，候选人将获得以下技能：（1）社交 流行病学方法;（2）空间流行病学;（3）患者报告的结果研究方法，因为它们 适用于社区感染。这些技能将有助于拉斐尔博士过渡到独立， 独特的定位，她解决多层次的因素，以改善社区发病的感染结果， 不同的人群。

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.