Epicenters III: Translational Research to Prevent Healthcare Associated Infection

描述（由申请人提供）：我们提出五个核心目标，评估减少医疗保健相关感染的新策略。这些目标包括两个T0，两个T1和一个T2翻译研究课题领域。我们选择这些主题是因为1)它们有很大的潜力可以改善健康结果，2)它们利用了我们之前在这些领域的工作，3)它们将加强我们的基础设施，提高我们对CDC可能要求震中解决的新主题的响应能力。两个主题涉及严重MRSA感染的预防：1)我们将通过比较致病性MRSA分离株和非致病性MRSA分离株的基因来鉴定MRSA的毒力基因。我们有能力处理来自300个纯种分离株的完整序列数据，为确定新疗法的靶点提供了独特的机会。这项工作建立在与麻省理工学院/哈佛大学博德研究所的遗传学家的现有合作基础上，并使用了现有的标本库。2)当莫匹罗星耐药导致后者无法使用时，我们将评估retapamulin局部去菌落的潜在效用。目前，尚无批准的用于MRSA去菌落的二线外用药物。这项T1工作将利用资助的随机对照试验研究长期非殖民化。两个主题涉及呼吸机护理并发症：3)我们将探讨氯己定用于胃净化的潜在用途，以减少呼吸机相关肺炎和其他医院感染的发生率，而不选择抗菌素耐药性。成功的T1研究将有助于对氯己定进行更全面的评估。4)我们将评估不同镇静药物，尤其是右美托咪定与呼吸机相关性肺炎风险的关系。本T0研究将为镇静管理作为预防医院获得性感染的策略建立证据基础，并利用我们与美国医院公司（HCA）（一家160多家医院组织）合作的独特电子数据资源，告知需要进行正式的临床试验。我们的最后一项研究5)将测试实时集群检测对医院院内疫情的规模、持续时间和数量的影响。T2研究将涵盖所有医院内病原菌，包括革兰氏阳性菌和革兰氏阴性菌，以及所有主要类型的医院内感染，包括血流、手术部位、尿路等。我们进一步描述了我们广泛的地方、区域和国家合作如何有助于建立现成的基础设施，以应对未来出现的医疗流行病学需求和项目。我们的综合网络包括三个州卫生部门，美国各地的许多成人和儿科设施，包括住院，养老院和门诊设施在内的区域人口实验室，以及一个大型多中心微生物实验室和健康信息系统。这些合作联盟是多年来富有成效的研究伙伴关系的高潮，并为卫生保健相关感染预防研究提供了强有力的响应系统。

DESCRIPTION (provided by applicant): We propose five core aims evaluating novel strategies to reduce healthcare associated infections. These aims include two T0, two T1, and one T2 translational research topic areas. We chose these topics because 1) they have high potential to lead to improvements in health outcomes, 2) they take advantage of our prior work in these domains, and 3) they will strengthen our infrastructure and improve our ability to respond to new topics CDC may ask the Epicenters to address. Two topics address prevention of serious MRSA infection: 1) We will identify virulence genes in MRSA by comparing the genes in pathogenic MRSA isolates to those in non- pathogenic isolates. Our ability to work with full sequence data from 300 pedigreed isolates provides a unique opportunity to identify targets for novel therapeutics. This T0 work builds on an existing collaboration with geneticists at the MIT/ Harvard Broad Institute and uses an existing specimen bank. 2) We will assess the potential utility of retapamulin for topical decolonization when mupirocin resistance makes the latter agent unusable. At present, there is no approved second line topical agent for MRSA decolonization. This T1 work will take advantage of a funded RCT studying long term decolonization. Two topics deal with complications of ventilator care: 3) We will explore the potential utility of chlorhexidine for gastric decontamination to reduce the incidence of ventilator-associated pneumonia and other nosocomial infections without selecting antimicrobial resistance. A successful T1 study will help position chlorhexidine for a fuller evaluation. 4) We will evaluate the relationship of different sedating agents, especially dexmedetomidine, with risk of ventilator associated pneumonia. This T0 study will build the evidence base for sedation management as a strategy to prevent hospital acquired infections and use the unique electronic data resources from our collaboration with Hospital Corporation of America (HCA), a 160+ hospital organization, to inform the need for a formal clinical trial. Our last study 5) will test the impact of real-time cluster detection on the size, duration, and number of nosocomial outbreaks in hospitals. This T2 study will cover all nosocomial pathogens, including Gram positive and Gram negative bacteria, and all major types of nosocomial infections, including bloodstream, surgical site, urinary tract, and others. We further describe how our extensive local, regional, and national collaborations contribute to a ready infrastructure to respond to future healthcare epidemiology needs and projects as they arise. Our comprehensive networks encompass three state health departments, numerous adult and pediatric facilities across the US, regional population laboratories including inpatient, nursing home, and outpatient facilities, as well as a large multi-center microbiology laboratory and health informatics system. These collaborative alliances are the culmination of productive research partnerships over many years and provide a robust response system for healthcare associated infection prevention research.