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

描述（由申请人提供）：我们对万古霉素耐药金黄色葡萄球菌（VRSA）出现的宿主和生物体前体的理解存在根本差距，这是一个主要的公共卫生问题。这一职业发展奖项将支持Emily Martin博士的进一步培训，因为她正在调查VRSA出现的关键前体：耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素肠球菌（VRE）的双重感染的流行病学和结果。该奖项将进一步推动马丁博士的长期目标，即加深我们对推动抗生素耐药感染在普通人群中传播的相关因素的理解。本申请的总体目标是建立一个独立的研究项目，以确定MRSA和VRE双重感染患者的危险因素和预后，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MRSA和VRE感染的关键临床和人口危险因素；(2)定义感染后不良后果的风险，包括培养后的住院时间

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.