Defining Precursors to VRSA Emergence: Epidemiology of MRSA & VRE Dual Infection

描述(由申请人提供)：对于万古霉素耐药金黄色葡萄球菌(VRSA)的出现，我们对宿主和机体前体的理解存在根本差距，VRSA是一个主要的公共卫生问题。该职业发展奖将支持艾米丽·马丁博士的进一步培训，因为她正在调查VRSA出现的一个关键先兆的流行病学和结果：由耐甲氧西林金黄色葡萄球菌(MRSA)和万古霉素耐药肠球菌(VRE)引起的双重感染。该奖项将进一步推进马丁博士的长期目标，即发展我们对推动抗生素耐药感染在普通人群中传播的相互关联因素的理解。这项应用的总体目标是建立一个独立的研究计划，以确定MRSA和VRE双重感染患者的危险因素和结果，以及感染微生物的特定分子特征和菌株类型。我们提出以下具体目标：(1)确定感染MRSA和VRE的关键临床和人口学风险因素；(2)确定感染后不良后果的风险，包括在 (1)将同时由MRSA和VRE引起的急性双重感染的患者与仅由MRSA或VRE引起的感染的患者进行比较；(3)确定感染超敏感的MRSA菌株和/或MRSA或VRE所含的促进细菌物种间耐药性转移的分子元件的风险因素。这项研究的一个显著优势是S，它将在密歇根州东南部进行，该地区是世界上VRSA患病率最高的地区，在专家导师(Keith Kaye博士和Michael Rybak博士)的支持下，以及在细菌感染特定主题的出色培训下进行。预期的结果是：1)确定将作为未来预防研究基础的关键风险因素；2)收集关于患者出院的详细的预期数据，这将确定改善护理的机会；以及3)通过表征导致临床VRE和MRSA分离株出现万古霉素耐药性的分子因素，确定最有可能感染VRSA的目标人群。这项拟议的研究与公共卫生有关，因为迫切需要更好地了解万古霉素耐药金黄色葡萄球菌(VRSA)出现的前体，特别是在底特律大都市地区。这项对MRSA和VRE双重感染的危险因素、特征和结果的流行病学研究是了解并最终防止未来出现万古霉素耐药性的关键一步。这项研究与NIAID的使命相关，因为它将对未来预防两种高度优先的生物的抗菌素耐药性和确定需要干预的关键患者群体产生积极影响。这项研究将导致整个NIH感兴趣的患者的结果得到改善，包括老年人口和患有慢性病的个人 疾病，通过检查宿主因素、耐药性的分子决定因素和多菌感染之间的相互作用。

DESCRIPTION (provided by applicant): There is a fundamental gap in our understanding of host and organism precursors to the emergence of vancomycin-resistant Staphylococcus aureus (VRSA), a major public health concern. This career development award will support the further training of Emily Martin, MPH PhD, as she investigates the epidemiology and outcomes of a key precursor to VRSA emergence: dual infection due to methicillin-resistant S. aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). The award will further Dr. Martin's long-term goal to evolve our understanding of the interrelated factors that drive the spread of antibiotic-resistant infections in the general population. The overall objective of this applicatio is to establish an independent research program to determine the risk factors and outcomes of patients with dual infection with MRSA and VRE as well as the specific molecular characteristics and strain types of the infecting organisms. We propose the following Specific Aims: (1) To identify the key clinical and demographic risk factors for infection with both MRSA and VRE; (2) To define the risk of post-infection adverse outcomes including length of stay following culture in patients with acute dual infections due to both MRSA and VRE compared to patients with infections due to MRSA or VRE alone; (3) To determine the risk factors for infection with hypersusceptible MRSA strains and/or MRSA or VRE containing molecular elements which facilitate the transfer of resistance between bacterial species. A notable strength of this study s that it will be performed in Southeast Michigan, the area with the highest prevalence of VRSA in the world, with the support of expert mentors (Drs. Keith Kaye and Michael Rybak) and excellent training in topics specific to bacterial infection. The expected outcomes are: 1) to identify key risk factors that will serve as a foundation for future prevention studies; 2) to collct detailed, prospective data on patient out- comes, which will identify opportunities to improve care; and 3) to identify a target population most at risk of VRSA infection through characterization of molecular elements that drive the emergence of vancomycin resistance in clinical VRE and MRSA isolates. The proposed research is relevant to public health because of the urgent need to better understand precursors to the emergence of vancomycin-resistant S. aureus (VRSA), particularly in the Detroit metro area. This epidemiologic study of the risk factors, characteristics, and outcomes of dual infections with MRSA and VRE is a key step in understanding and ultimately preventing future emergence of vancomycin resistance. This research is relevant to the mission of the NIAID in that it will have a positive impact on the futue prevention of antimicrobial resistance in two high-priority organisms and on the identification of key patient groups for intervention. This research will lead to improvement of outcomes in patients of interest throughout the NIH, including elderly populations and individuals with chronic disease, by examining the interaction between host factors, molecular determinants of resistance, and polymicrobial infections.