Mentoring and patient-oriented research in antimicrobial resistance

申请人简介(申请人提供)：申请人为传染病系医学副教授、生物统计与流行病学系流行病学副教授、宾夕法尼亚大学医学院临床流行病学与生物统计学中心高级学者。他是一位久负盛名的临床研究员，作为同行审查的联邦资金的首席调查员，有着广泛的记录。这位候选人开发了一项非常成功和创新的以患者为导向的研究计划，重点是抗菌素耐药性的流行病学。他也有明确的成就记录，并致力于指导下一代以患者为导向的研究人员。他通过扩展研究培训计划、课程开发和指导以及个人指导，在建立临床研究培训机会方面发挥了关键作用。宾夕法尼亚大学致力于为申请者提供以患者为导向的研究和指导的强大环境，包括多个机构培训赠款、机构临床和翻译科学奖(CTSA)计划、非常成功的临床流行病学理学硕士(MSCE)培训计划，以及出色的实验室、生物统计学和数据管理支持。申请人目前的R01之一是一项前瞻性队列研究，旨在调查长期护理机构(LTCF)居民中耐氟喹诺酮类大肠杆菌(FQREC)在胃肠道定植的流行病学。虽然这项研究集中在临床FQREC感染最终发展的几个关键步骤上，但这种定植途径的最早方面(即限制E.Constraint从FQ敏感到FQ耐药的进展)仍未被研究。阐明FQ耐药性演变的这些早期步骤，对于确定可能需要干预的关键患者变量(例如抗生素使用)和机体变量(例如毒力因素)至关重要。事实上，这一应用代表了一个强大的人体模型，用于研究临床环境中抗生素耐药性的演变。凭借其成熟的基础设施和独特的纵向患者队列，正在进行的LTCFR01研究提供了一个独特的机会来回答本申请中提出的重要新问题。此外，拟议的新研究将极大地扩大正在进行的长期合作框架R01的范围。这一独特的研究基础设施也将为申请者的学员提供宝贵的研究和指导机会。来自K24的支持将使候选人能够大幅扩大他的研究计划，并在以患者为导向的专注于抗菌素耐药性的研究中取得相当大的个人指导成功的记录。

DESCRIPTION (provided by applicant): The applicant is an Associate Professor of Medicine in the Division of Infectious Diseases, an Associate Professor of Epidemiology in the Department of Biostatistics and Epidemiology, and a Senior Scholar at the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania School of Medicine. He is an established clinical investigator with an extensive track record as the Principal Investigator of peer- reviewed federal funding. The candidate has developed a highly successful and innovative patient-oriented research program focusing on the epidemiology of antimicrobial resistance. He also has a clear record of accomplishment and commitment to mentoring the next generation of patient-oriented researchers. He has played a critical role in building clinical research training opportunities through expansion of research training programs, course development and instruction, and individual mentoring. The University of Pennsylvania is committed to providing the applicant with a strong environment for patient-oriented research and mentoring, including multiple institutional training grants, an institutional Clinical and Translational Science Award (CTSA) program, an extraordinarily successful Master of Science in Clinical Epidemiology (MSCE) training program, and outstanding laboratory, biostatistics, and data management support. One of the applicant's current R01s is a prospective cohort study examining the epidemiology of gastrointestinal tract colonization with fluoroquinolone-resistant Escherichia coli (FQREC) in long-term care facility (LTCF) residents. While this study focuses on several critical steps in the ultimate development of clinical FQREC infection, the earliest aspects of this pathway of colonization (i.e., the progression of an E. constrain from FQ-susceptible to FQ-resistant) remain unstudied. Elucidation of these earlier steps in the evolution of FQ resistance is critical in identifying key patient variables (e.g., antibiotic use) and organism variables (e.g., virulence factors) which may be amenable to intervention. Indeed, this application represents a powerful human model for studying evolution of antibiotic resistance in the clinical setting. With its established infrastructure and unique longitudinal patient cohort, the ongoing LTCF R01 study provides a distinctive opportunity to answer the important new questions proposed in this application. Furthermore, the new proposed research will expand considerably the scope of the ongoing LTCF R01. This unique research infrastructure will also offer valuable research and mentoring opportunities for the applicant's trainees. Support from the K24 will allow the candidate to substantially expand his research program and considerable track record of successful individual mentoring in patient-oriented research focused on antimicrobial resistance.