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

描述（由申请人提供）：我们对耐万古霉素金黄色葡萄球菌（VRSA）出现的宿主和生物体前体的理解存在根本性差距，VRSA是一个主要的公共卫生问题。这个职业发展奖将支持进一步培训艾米丽马丁，公共卫生硕士博士，因为她调查的流行病学和结果的一个关键前兆VRSA出现：双重感染由于耐甲氧西林S。金黄色葡萄球菌（MRSA）和万古霉素耐药肠球菌（VRE）。该奖项将进一步推进马丁博士的长期目标，即发展我们对推动耐药性感染在普通人群中传播的相互关联因素的理解。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双重感染患者的风险因素和结局，以及感染微生物的特定分子特征和菌株类型。我们提出了以下具体目标：（1）确定MRSA和VRE感染的关键临床和人口统计学风险因素;（2）确定感染后不良结局的风险，包括培养后的住院时间， 与仅由MRSA或VRE引起的感染患者相比，由MRSA和VRE引起的急性双重感染患者;（3）确定感染高敏感性MRSA菌株和/或含有促进细菌物种之间抗性转移的分子元件的MRSA或VRE的风险因素。 这项研究的一个显著优势是，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，并得到专家导师（基思凯博士和迈克尔·里巴克博士）的支持，以及细菌感染特定主题的出色培训。预期成果是：1）确定关键风险因素，作为未来预防研究的基础; 2）收集患者结局的详细前瞻性数据，以确定改善护理的机会; 3）通过表征临床VRE和MRSA分离株中导致万古霉素耐药性出现的分子要素，确定最有可能发生VRSA感染的目标人群。由于迫切需要更好地了解万古霉素耐药链球菌出现的前体，因此拟议的研究与公共卫生有关。金黄色葡萄球菌（VRSA），特别是在底特律都会区。这项关于MRSA和VRE双重感染的危险因素、特征和结局的流行病学研究是了解并最终预防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优先级微生物的抗菌素耐药性以及确定需要干预的关键患者群体产生积极影响。这项研究将改善整个NIH感兴趣的患者的结局，包括老年人群和慢性病患者。 疾病，通过检查宿主因素，耐药性的分子决定因素和多微生物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.