Using Big-Data to Identify & Prevent Transmission of Carbapenem-Resistant Enterobacteriaceae within VHA

利用大数据进行识别

• 批准号: 10295148
• 负责人: Andrew Chou
• 金额: --
• 依托单位: MICHAEL E DEBAKEY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10295148
• 关键词: Adverse event; Antibiotic Resistance; Antibiotic Therapy; Antibiotic-resistant organism; Antibiotics; Antimicrobial Resistance; Area; Awareness; Bacteria; Bacterial Antibiotic Resistance; Big Data; Big Data Methods; Bioinformatics; Biometry; Carbapenems; Categories; Ceftazidime; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; Clinical Trials; Clostridium difficile; Combined Antibiotics; Combined Modality Therapy; Communicable Diseases; Complex; Dangerousness; Data; Data Science; Databases; Dedications; Disease Outbreaks; Doctor of Philosophy; Educational Background; Effectiveness; Enterobacter cloacae; Enterobacteriaceae Infections; Environment; Faculty; Formularies; Fostering; Future; Gram-Negative Bacteria; Guidelines; Health; Health Care Costs; Health care facility; Hospitals; Individual; Infection; Infection prevention; Intervention; Junior Physician; K-Series Research Career Programs; Klebsiella pneumoniae; Knowledge; Lead; Master of Science; Mathematics; Measures; Medical center; Medicine; Mentors; Meropenem; Microbiology; Modeling; Morbidity - disease rate; Oncology; Outcome; Patients; Performance; Persons; Physicians; Pilot Projects; Population; Prevalence; Prevention; Prevention program; Productivity; Public Health; Publications; Publishing; Recording of previous events; Regimen; Reporting; Research; Research Personnel; Research Priority; Research Training; Resistance; Risk; Risk Factors; Safety; Scientist; Sepsis; Specialist; Statistical Models; Systems Biology; Techniques; Testing; Training; Training and Education; Treatment outcome; United States; United States Department of Veterans Affairs; Veterans; Veterans Health Administration; Virulence Factors; Work; acute care; antibiotic resistant infections; carbapenem resistance; carbapenem-resistant Enterobacteriaceae; carbapenemase; career; clinical risk; college; combat; comorbidity; computer program; design; evidence base; experience; high risk; improved; innovation; microbial genomics; mid-career faculty; military veteran; mortality; multi-drug resistant pathogen; nephrotoxicity; novel; optimal treatments; ototoxicity; post-doctoral training; predictive tools; prevent; prospective; resistant Klebsiella pneumoniae; risk stratification; screening; side effect; skills; statistics; success; surveillance strategy; tool; transmission process; virus related cancer

This proposal is designed to provide the necessary knowledge, skills, and experience required to facilitate the transition of Andrew Chou, MD, from junior to independent investigator in the field of antibiotic- resistant infections. Dr. Chou is a well-trained infectious diseases specialist with graduate-level education and postdoctoral training in microbiology and microbial genomics. He has been studying multidrug-resistant organisms (MDRO) since 2009 and has a demonstrated history of dedication to a career in research and to the Veterans Health Administration (VHA). Dr. Chou has identified a mentoring committee consisting of senior investigators who have demonstrated success in mentoring junior investigators to independence. Barbara W. Trautner, MD, PhD, associate professor of Medicine (Infectious Diseases) and faculty at the Center for Innovations in Quality, Effectiveness, and Safety (IQuESt) at the Houston VA and Baylor College of Medicine (BCM), will serve as the primary mentor. The co-mentors are: 1) Lynn Zechiedrich, PhD, an expert in mechanisms of antibiotic resistance and systems biology; 2) Elizabeth Chiao, MD, MPH, an expert in using large databases to study viral-associated malignancies and board-certified in both infectious diseases and oncology; 3) Richard Sucgang, PhD, an expert in bioinformatics of antibiotic resistance; and 4) Peter Richardson, PhD, an expert in mathematical statistics and probability modeling. Dr. Chou has a history of productivity with the primary mentor and multiple co-mentors, including publications in studying Klebsiella pneumoniae virulence factors within VHA, bloodstream infections due to gram-negative bacteria, and an outbreak of carbapenem-resistant Enterobacteriaceae (CRE). To expand his skill set, Dr. Chou will pursue a Master of Science in biostatistics, studying the data science track and biostatistics. Antibiotic resistance is an important health concern in the United States and within VHA. CRE is 1 of the most dangerous antibiotic-resistant organisms because nearly half of all patients with CRE bloodstream infections die. CRE infections are resistant to all or nearly all antibiotics, often are treated with last-line antibiotics that are associated with severe side-effects, and can lead to hospital outbreaks. CRE infections incur significant morbidity and mortality, yet optimal prevention and treatment of CRE are unknown. The published report, Establishing the Research Agenda for Preventing Transmission of MDRO in Acute-Care Settings in VHA, identified studying screening strategies to identify Veterans asymptomatically colonized with CRE as a research priority. Determining the optimum treatment of CRE is challenging because patients with CRE infections often have complex comorbidities that exclude them from clinical trials. The project objective is to combat CRE within VHA by (1) developing novel, targeted surveillance strategies that identify Veterans at high risk for CRE colonization; and (2) identifying which antibiotic regimens are associated with the most desirable clinical outcomes (ie, clinical cure without adverse events) in Veterans with CRE infections. Aim 1 will create the VHA CRE colonization risk-stratification tool for the national VHA population using bioinformatics to analyze large-scale clinical VHA databases. Aim 2 will develop best practices for treatment of CRE bloodstream infection by applying biostatistical techniques to VHA databases to compare newer antibiotics to standard therapy, monotherapy vs. combination antibiotic therapy, and short- course vs. prolonged-course duration of antibiotic therapy. Aim 3 will be to conduct a pilot intervention of 3 different CRE surveillance strategies: passive surveillance, surveillance targeted by clinical risk factors, and surveillance targeted to patients with Clostridioides difficile infection. The environment at BCM is ideal for fostering the training of junior physician investigators. Dr. Chou will benefit from strong institutional support, outstanding mentoring, and a clear path to independence.

本建议书旨在提供必要的知识、技能和经验， 促进Andrew Chou，MD从初级到抗生素领域独立研究者的转变- 耐药性感染周博士是一位训练有素的传染病专家，具有研究生水平的教育， 微生物学和微生物基因组学博士后培训。他一直在研究耐多药的 自2009年以来，他一直致力于研究事业， 退伍军人健康管理局（VHA）。周博士已经确定了一个由资深 在指导初级调查员独立方面取得成功的调查员。芭芭拉·W Trautner，医学博士，博士，医学（传染病）副教授和中心的教师， 质量，有效性和安全性创新（IQuESt）在休斯敦VA和贝勒医学院 (BCM)，将担任主要导师。共同导师是：1）林恩Zechiedrich，博士，专家在 抗生素耐药性和系统生物学机制; 2）Elizabeth Chiao，医学博士，公共卫生硕士，使用 研究病毒相关恶性肿瘤的大型数据库， 肿瘤学; 3）Richard Sucgang博士，抗生素耐药性生物信息学专家; 4）Peter Richardson博士是数理统计和概率建模方面的专家。周医生有 主要导师和多位共同导师的生产力，包括研究克雷伯氏菌的出版物 VHA内的肺炎毒力因子、革兰氏阴性菌引起的血流感染以及 碳青霉烯类耐药肠杆菌科（CRE）爆发。为了扩展他的技能，周博士将继续学习 生物统计学硕士，学习数据科学和生物统计学。 抗生素耐药性是美国和VHA内部的一个重要健康问题。CRE为1 最危险的抗药性微生物，因为近一半的CRE患者的血液 感染死亡。CRE感染对所有或几乎所有抗生素都有耐药性，通常用最后一线治疗。 抗生素有严重的副作用，并可能导致医院爆发。 CRE感染导致显著的发病率和死亡率，但CRE的最佳预防和治疗 是未知的。发表的报告《建立预防MDRO传播的研究议程》 在VHA的急性护理环境中，确定了研究筛查策略以无症状地识别退伍军人 将CRE作为研究重点。确定CRE的最佳治疗具有挑战性，因为 患有CRE感染的患者通常具有复杂的合并症，这将他们排除在临床试验之外。 该项目的目标是通过（1）开发新的、有针对性的监测来打击VHA内的CRE 识别CRE定植高风险退伍军人的策略;以及（2）确定哪些抗生素方案 与退伍军人中最理想的临床结局（即临床治愈，无不良事件）相关 CRE感染。目标1将为国家VHA创建VHA CRE殖民风险分层工具 使用生物信息学分析大规模临床VHA数据库。目标2将发展得最好 通过将生物统计技术应用于VHA数据库来治疗CRE血流感染的实践， 比较新的抗生素与标准治疗，单药治疗与联合抗生素治疗，以及短期- 抗生素治疗的疗程与延长疗程。目标3将是进行一次试点干预， 不同的CRE监测策略：被动监测、针对临床风险因素的监测，以及 针对艰难梭菌感染患者的监测。 环境是理想的，以促进初级医师研究人员的培训。周医生会 受益于强有力的机构支持、出色的指导和明确的独立道路。