National surveillance of emerging MDR in pediatric Enterobacteriaceae infections

项目总结/摘要 抗菌素耐药性日益严重的问题已得到充分认识。多重耐药感染 微生物是具有挑战性的治疗，并与增加的发病率，死亡率和支出， 医疗资源。虽然人们对了解流行病学的关注很多， 革兰氏阳性菌的耐药性，尤其是耐甲氧西林金黄色葡萄球菌， 了解革兰氏阴性菌多重耐药的流行病学，特别是在儿科。 我们的初步数据显示，质粒传播的， 我们儿科中心肠杆菌科的广谱β-内酰胺耐药（PBLR）。这种类型的 耐药性包括质粒携带的AmpC-、ESBL-和碳青霉烯酶型决定簇， 这既是因为它限制了治疗感染的抗菌剂，也是因为质粒很容易 可以在生物体之间转移，从而对耐药性的快速传播造成威胁。我们建议多中心 描述中国儿童PBLR的国家分子和流行病学趋势的试点项目 肠杆菌科 目标1.估计质粒传播的广谱β-内酰胺类耐药（PBLR）的患病率， 描述相应分子决定簇和质粒类型的频率分布， 来自美国4个医疗中心的临床儿科肠杆菌科分离株。 2.明确大肠杆菌的克隆背景和毒力特性。显示PBLR的大肠杆菌分离株 与对照E.不含PBLR的大肠杆菌菌株。 3.定义与PBLR相关的人口统计学、临床和细菌因素， 儿科患者肠杆菌科感染。 方法.一个由4家儿科医院组成的联合体参与了该项目。每个研究中心，通过常规临床试验 护理，将确定具有潜在指示PBLR的耐药模式的肠杆菌科。这些分离株 （沿着非PBLR对照分离株）以及感染患者的人口统计学和临床数据将被 送到西雅图儿童医院，在那里将进行生物体的进一步表征和数据分析。 项目的预期成果。该项目将确定儿科中PBLR耐药的范围， 全国范围内。这些信息有可能为严重的 儿童细菌感染。它还将提供来自临床数据综合分析的新信息 从人类宿主，菌株背景和细菌宿主的毒力，以及 阻力这将为设计未来的干预性研究提供所需的信息， 防止PBLR抗性。

PROJECT SUMMARY/ABSTRACT The growing problem of antimicrobial resistance is well recognized. Infections with multi-drug resistant organisms are challenging to treat, and are associated with increased morbidity, mortality, and expenditure of healthcare resources. While much attention has been directed at understanding the epidemiology of resistance in Gram-positive organisms, especially methicillin-resistant Staphylococcus aureus, much less is known about the epidemiology of multi-drug resistance in Gram-negative organisms, particularly in pediatrics. Our preliminary data demonstrate statistically significant and very worrisome increases in plasmid-borne, broad-spectrum ¿-lactam resistance (PBLR) in Enterobacteriaceae at our pediatric center. This type of resistance includes plasmid-borne AmpC-, ESBL-, and carbapenemase-type determinants, and is concerning both because it limits the antimicrobials available to treat infections and because plasmids are readily transferable between organisms, creating a threat for rapid spread of resistance. We propose a multicenter pilot project to describe national molecular and epidemiological trends in pediatric PBLR in Enterobacteriaceae. Aims 1. To estimate the prevalence of plasmid-borne, broad-spectrum ¿-lactam resistance (PBLR), and to describe frequency distributions of the respective molecular determinants and plasmid types, among clinical pediatric Enterobacteriaceae isolates from 4 medical centers across the U.S. over time. 2. To define the clonal background and virulence properties of E. coli isolates demonstrating PBLR versus control E. coli isolates without PBLR. 3. To define the demographic, clinical, and bacterial factors associated with PBLR in Enterobacteriaceae infections in pediatric patients. Methods. A consortium of 4 pediatric hospitals is involved in this project. Each site, through routine clinical care, will identify Enterobacteriaceae with resistance patterns potentially indicative of PBLR. These isolates (along with non-PBLR control isolates) and demographic and clinical data from the infected patients will be sent to Seattle Children's, where further characterization of the organisms and data analyses will take place. Expected Outcomes of the Project. This project will define the scope of PBLR resistance in pediatrics on a national scale. This information has the potential to inform treatment, especially empiric treatment, of serious bacterial infections in children. It will also provide novel information from integrated analyses of clinical data from the human host, strain background and virulence of the bacterial host, and the molecular determinants of resistance. This will provide needed information for the design of future interventional studies aimed at preventing PBLR resistance.