Mentoring and patient-oriented research in antimicrobial resistance

描述（由申请人提供）：申请人是传染病系医学副教授、生物统计学和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和生物统计学中心高级学者。他是一位成熟的临床研究者，作为同行评审的联邦资金的主要研究者，有着广泛的跟踪记录。候选人已经开发了一个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。他也有一个明确的成就记录和承诺，指导下一代以病人为导向的研究人员。他通过扩大研究培训计划，课程开发和教学以及个人指导，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人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，机构临床和转化科学奖（CTSA）计划，非常成功的临床流行病学（MSCE）培训计划科学硕士，以及出色的实验室，生物统计学和数据管理支持。申请人当前的R01之一是一项前瞻性队列研究，旨在检查长期护理机构（LTCF）居民中氟喹诺酮类耐药大肠埃希菌（Escherichia coli，Escherichia REC）胃肠道定植的流行病学。虽然这项研究的重点是在临床ESPREC感染的最终发展的几个关键步骤，最早的方面，这一途径的殖民（即，一个E.从对细菌敏感到对细菌抗性的限制）仍然未被研究。阐明FQ耐药性演变中的这些早期步骤对于确定关键患者变量（例如，抗生素使用）和生物体变量（例如，毒力因子），其可适于干预。事实上，这一应用代表了一个强大的人类模型，用于研究临床环境中抗生素耐药性的演变。凭借其已建立的基础设施和独特的纵向患者队列，正在进行的LTCF R01研究为回答本申请中提出的重要新问题提供了独特的机会。此外，新提出的研究将大大扩大正在进行的LTCF R01的范围。这种独特的研究基础设施也将为申请人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展他的研究计划，并在以患者为导向的研究中成功地进行个人指导，重点是抗菌素耐药性。相关性（见说明）：抗菌素耐药性的急剧增加威胁着我们最常用的抗生素。本申请中提出的研究将促进我们对驱动阻力的力量的理解，从而确定遏制阻力进一步出现的策略。来自K24奖的支持将为劳滕巴赫博士提供足够的时间来扩大他的研究计划，并建立在他在以患者为导向的研究中成功指导的良好记录基础上，重点关注抗菌素耐药性。

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. RELEVANCE (See instructions): Dramatic increases in antimicrobial resistance threaten our most commonly used antibiotics. The research proposed in this application will advance our understanding of the forces driving resistance, thereby identifying strategies to curb further emergence of resistance. Support from a K24 award will provide Dr. Lautenbach with sufficient time to expand his research program and build on his considerable track record of successful mentoring in patient-oriented research focused on antimicrobial resistance.