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

描述（由申请人提供）：在美国，由耐多药微生物（mdro）引起的感染每年导致10万人死亡，每年花费美国医疗保健系统超过300亿美元，越来越普遍，经常治疗不当，并且正在蔓延到社区环境。因此，这些感染被疾病预防控制中心贴上了“公共卫生危机”的标签。尽管美国的大多数护理是在小型社区医院提供的，但对社区环境中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，社区医院在耐药性的出现和传播中所起的作用仍然未知。PI的长期目标是成为一个独立的临床医生和科学家，在MDRO感染的临床和分子流行病学方面进行以患者为导向的研究（POR）。为了实现这一目标，PI将采用多方面的计划来获得分子基因分型技能，这将增强他在临床流行病学方面的专业知识，包括来自共同导师的密切监督，来自国家专家科学顾问委员会的高级指导，“动手”实验室培训，教学类工作，以及完成此处概述的POR。这项研究将利用a)杜克大学感染控制外展网络（DICON），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，生物库和分子测试基础设施，更好地了解社区医院的mdro。该项目的具体目标是：1)在10家社区医院住院的大型、前瞻性确定的患者队列中，确定由mdro引起的血流感染（bsi）的临床流行病学；2)建立临床生物信息库，收集社区医院住院的经前瞻性鉴定的mdro感染患者；3)利用新建立的生物库，确定并比较耐多药e感染患者的临床和分子流行病学。使用特定的分子技术，如聚合酶链反应（PCR）、脉冲场凝胶电泳（PFGE）和重复基因外回文(rep)-PCR，将社区医院的大肠杆菌、耐多药肺炎克雷伯菌或耐甲氧西林金黄色葡萄球菌（MRSA）转移到三级护理医院的患者。拟议研究的完成将导致a)迄今为止对社区医院耐多药bsi患者进行最完整的分析；b)建立和验证一个强大的、完全独特的研究基础设施，对一个独特的、重要的患者群体进行临床和分子POR；c)证明社区医院耐多药的重大负担；(d)证明社区医院作为重要病原体中耐多药耐药性发展来源的重要性。多药耐药菌（mdro）引起的感染导致不良的患者结果，越来越普遍，并且经常治疗不当。然而，对社区环境（如社区医院）中mdro的临床和分子流行病学知之甚少。利用杜克大学感染控制扩展网络的独特研究资源，我建议：1)确定社区医院因耐多药病原体引起的血液感染的不当治疗和结果的风险因素；2)在创建新的前瞻性生物库后，确定并比较社区医院与三级保健医院耐多药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.