Clinical and Molecular Epidemiology of Multidrug-Resistant Organisms in a Communi

描述(申请人提供)：由多药耐药生物(MDRO)引起的感染在美国每年导致100,000人死亡，每年给美国医疗系统造成超过300亿美元的损失，越来越常见，经常受到不适当的治疗，并正在蔓延到社区。因此，这些感染已被疾控中心贴上了“公共卫生危机”的标签。尽管美国的大多数护理是由小型社区医院提供的，但人们对社区环境中MDRO的临床和分子流行病学知之甚少。很少有研究提供关于这些病原体的临床和分子数据，在社区医院进行的研究就更少了。因此，社区医院在耐药性出现和传播中的作用仍不清楚。PI的长期目标是成为一名独立的临床医生-科学家，对MDRO感染的临床和分子流行病学进行以患者为中心的研究(POR)。为了实现这一目标，PI将使用一个多方面的计划来获取分子基因分型技能，这将增强他在临床流行病学方面的专业知识，包括共同导师的密切监督、由国家专家组成的科学顾问委员会的高级指导、“动手”实验室培训、授课课堂工作以及完成本文概述的POR。这项研究将利用a)杜克感染控制外展网络(DICON)，这是一个由39家社区医院组成的独特研究资源，以及b)先前存在的POR、生物库和分子检测基础设施，来更好地了解社区医院中的MDRO。该项目的具体目标是1)在10家社区医院入院的大量预期确定的患者队列中确定MDRO引起的血流感染(BSI)的临床流行病学；2)从社区医院入院的预期确定的MDRO感染患者创建临床生物库；以及3)使用新创建的生物库，确定和比较MDR-E感染患者的临床和分子流行病学。利用特定的分子技术，如聚合酶链式反应(PCR)、脉冲场凝胶电泳(PFGE)和重复基因外回文(REP)-PCR，将社区医院中的大肠埃希菌、耐多药肺炎克雷伯菌或耐甲氧西林金黄色葡萄球菌(MRSA)分发给三级护理医院的患者。拟议研究的完成将导致a)对社区医院中的MDR-BSI患者进行迄今为止最完整的分析；b)创建和验证一个强大的、完全独特的研究基础设施，以对一个独特的、重要的患者群体进行临床和分子POR；c)展示社区医院MDR的重大负担；以及d)证明社区医院作为重要病原体中MDR发展的来源的重要性。由多药耐药菌(MDRO)引起的感染会导致不良的患者结局，这种情况越来越普遍，而且经常得到不适当的治疗。然而，关于MDRO在社区环境中的临床和分子流行病学知之甚少，例如社区医院。利用杜克大学感染控制外展网络中的独特研究资源，我建议1)确定社区医院由于MDR病原体引起的血流感染的不适当治疗和预后的风险因素，以及2)在创建新的、预期的生物信息库之后，确定并比较社区医院和三级护理医院的MDRO患者的临床和分子流行病学。

DESCRIPTION (provided by applicant): Infections due to multidrug-resistant organisms (MDROs) lead to 100,000 deaths each year in the US, cost the US healthcare system more than $30 billion annually, are increasingly common, are frequently treated inappropriately, and are spreading to community settings. As a result, these infections have been labeled as a "public health crisis" by the CDC. Little is known about the clinical and molecular epidemiology of MDROs in community settings, despite the fact that the majority of care in the US is provided in small community hospitals. Few studies have provided both clinical and molecular data on these pathogens and even fewer have been performed in community hospitals. Thus, the role of the community hospital in the emergence and dissemination of resistance remains unknown. The long-term goal of the PI is to become an independent clinician-scientist performing patient-oriented research (POR) on the clinical and molecular epidemiology of MDRO infections. To achieve this goal, the PI will use a multi-faceted plan to acquire molecular genotyping skills that will enhance his expertise in clinical epidemiology, including close oversight from co-mentors, senior-level guidance from a scientific advisory board of national experts, "hands-on" laboratory training, didactic class work, and completion of POR as outlined herein. This study will provide a better understanding of MDROs in community hospitals using a) the Duke Infection Control Outreach Network (DICON), a unique research resource consisting of 39 community hospitals, and b) previously existing POR, biorepository, and molecular testing infrastructure. The specific aims of the project are to 1) determine the clinical epidemiology of bloodstream infections (BSIs) due to MDROs in a large, prospectively-identified cohort of patients admitted to 10 community hospitals; 2) create a clinical biorepository from prospectively identified patients with infections due to MDROs admitted to a community hospital; and 3) using the newly created biorepository, determine and compare the clinical and molecular epidemiology of patients with infections due to MDR-E. coli, MDR-Klebsiella pneumoniae, or methicillin-resistant Staphylococcus aureus (MRSA) in a community hospital to patients in a tertiary care hospital using specific molecular techniques such as polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE), and repetitive extragenic palindromic (rep)-PCR. The completion of the proposed research will lead to a) the most complete analysis of patients with MDR-BSI in community hospitals to date; b) the creation and validation of a robust, completely unique research infrastructure to perform clinical and molecular POR on a unique, important patient group; c) demonstration of the significant burden of MDR in community hospitals; and d) demonstration of the importance of community hospitals as a source for development of MDR among important pathogens. Infections due to multidrug-resistant organisms (MDROs) lead to adverse patient outcomes, are increasingly common, and are frequently treated inappropriately. Little is known, however, about the clinical and molecular epidemiology of MDROs in community settings, such as community hospitals. Using a unique research resource in the Duke Infection Control Outreach Network, I propose 1) to determine risk factors for inappropriate treatment of and outcomes from bloodstream infections due to MDR-pathogens in community hospitals and 2) after creation of a new, prospective biorepository, to determine and compare the clinical and molecular epidemiology of patients with MDROs in a community hospital to patients in a tertiary care hospital.