Epicenters III: Translational Research to Prevent Healthcare Associated Infection

描述（由申请人提供）：我们提出了五个核心目标，评估减少医疗相关感染的新策略。这些目标包括两个T0，两个T1和一个T2翻译研究主题领域。我们选择这些主题是因为1）它们具有很大的潜力，可以改善健康结果，2）它们利用了我们在这些领域的先前工作，3）它们将加强我们的基础设施，提高我们应对CDC可能要求Epicenters解决的新主题的能力。两个主题解决了严重MRSA感染的预防：1）我们将通过比较致病性MRSA分离株与非致病性分离株中的基因来鉴定MRSA中的毒力基因。我们能够处理来自300个家系分离株的全序列数据，这为确定新疗法的靶点提供了独特的机会。这项T0工作建立在与麻省理工学院/哈佛布罗德研究所遗传学家的现有合作基础上，并使用现有的标本库。2)我们将评估当莫匹罗星耐药性使瑞他莫林无法使用时，瑞他莫林用于局部去殖民化的潜在效用。目前，没有批准的用于MRSA去殖民化的二线局部药物。这项T1工作将利用一项研究长期非殖民化的受资助RCT。两个主题涉及呼吸机护理的并发症：3）我们将探讨洗必泰用于胃净化的潜在效用，以减少呼吸机相关性肺炎和其他医院感染的发生率，而不选择抗菌药物耐药性。一个成功的T1研究将有助于定位洗必泰进行更全面的评估。4)我们将评估不同镇静剂，尤其是右美托咪定与呼吸机相关性肺炎风险的关系。这项T0研究将建立镇静管理的证据基础，作为预防医院获得性感染的策略，并使用我们与美国医院公司（HCA）（一个拥有160多家医院的组织）合作的独特电子数据资源，以告知需要正式的临床试验。我们的最后一项研究将测试实时集群检测对医院内爆发的规模、持续时间和数量的影响。本T2研究将涵盖所有医院内病原体，包括革兰氏阳性和革兰氏阴性细菌，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一个现成的基础设施，以应对未来的医疗流行病学需求和项目。我们的综合网络包括三个州的卫生部门，美国各地的众多成人和儿科设施，区域人口实验室，包括住院，疗养院和门诊设施，以及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，并为医疗保健相关的感染预防研究提供了一个强大的响应系统。

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.