Households as Reservoirs of Community-Acquired Extended-Spectrum Beta-Lactamase-producing Enterobacterales

项目摘要 肠杆菌属对多种抗生素的耐药性越来越强，使其成为全球流行的公共卫生 威胁。产超广谱β-内酰胺酶肠杆菌(ESBL Ent)感染 仅限于医疗保健环境，但在过去20年中，感染人数显著增加 发生在其他健康的儿童和成年人身上，没有事先接触过医疗保健。这些是由社区获得的 (CA)ESBL Ent菌株在流行病学和基因上与医疗保健获得的菌株不同，但 同样与严重感染、费用高、住院时间长、随后的医院传播有关，以及 糟糕的结果。重要的是，ESBL Ent已从医疗保健环境中恢复并链接到 人类中的传播事件，但家庭环境对社区获得者的贡献 感染情况尚不清楚。我们最近令人惊讶地发现，在儿童中，ESBL Ent感染是4-34倍 可能是社区获得性感染，而不是感染敏感菌株。这一看似自相矛盾的现象凸显了 对抗生素耐药基因的传播动力学、储存库和来源的认识存在严重差距 (Args)在CA-ESBL Ent.这些信息是为中断社区传播的战略提供信息所必需的。 拟议的研究将产生关于基于社区的耐药性暴露的重要新知识。 通过检查健康人和潜在的家庭环境来源携带的细菌。这项建议 有两个目的：1)在健康儿童家庭中，测量ESBL Ent的患病率和分子生态学 环境污染；以及2)测量健康个体中ESBL Ent定植的流行率 并探索与携带ESBL Ent有关的个人水平的流行病学因素。一个 人类和人类体内细菌和ARGs的全面培养和基于分子的表征 环境样本将评估可能促进抗药性菌株类型传播的家庭水库。 该群落现在是ESBL Ent毒力株传播到 医院，给临床医生和感染预防专家带来了新的挑战。为了有效地缓解 ESBL Ent菌株在医疗保健和社区环境中的传播，我们必须首先了解流行情况 在健康的社区居住的个体中，确定与ESBL Ent定植相关的因素，并确定 环境表面污染在这些病原体传播中的意义。《知识》 通过拟议的调查获得的信息可以提供新的感染预防策略，以减少 ESBL Ent在社区中的负担。像我们这样导致预防性进展的调查将会受益 大量的患者，并对医疗保健的利用和支出产生积极影响。这项研究 将描述关键的家庭ESBL Ent储集层的特征，并对ARG的潜在途径产生有价值的见解 获取和传播途径，为后续调查和有针对性的干预提供信息。

Project Summary Enterobacterales are increasingly resistant to multiple antibiotics, making them a global epidemic public health threat. Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL Ent) infections were historically limited to healthcare settings, but over the past two decades there have been significant increases in infections occurring in otherwise healthy children and adults without prior healthcare contact. These community-acquired (CA) ESBL Ent strains are epidemiologically and genetically distinct from healthcare-acquired strains, yet similarly associated with severe infections, high costs, long hospital stays, subsequent nosocomial spread, and poor outcomes. Importantly, ESBL Ent have been recovered from the healthcare environment and linked to transmission events in humans, yet the contribution of the household environment to community-acquired human infection is unknown. We recently discovered surprisingly that in children, ESBL Ent infections were 4-34x more likely to be community-acquired than were infections with susceptible strains. This seeming paradox highlights critical gaps in knowledge of transmission dynamics, reservoirs and sources of antibiotic resistance genes (ARGs) in CA-ESBL Ent. Such information is needed to inform strategies to interrupt community transmission. The proposed studies will yield important new knowledge about community-based exposures to resistant bacteria by examining carriage in healthy persons and potential household environmental sources. The proposal has two aims: 1) In households of healthy children, measure the prevalence and molecular ecology of ESBL Ent environmental contamination; and 2) Measure the prevalence of ESBL Ent colonization in healthy individuals within households and explore individual level epidemiological factors associated with carriage of ESBL Ent. A comprehensive culture- and molecular based characterization of bacteria and ARGs within human and environmental samples will assess household reservoirs that may facilitate transmission of resistant strain types. The community is now an important and expanding reservoir for the spread of virulent ESBL Ent strains into hospitals, posing new challenges to clinicians and infection prevention specialists. To effectively mitigate the spread of ESBL Ent strains in both healthcare and community settings, we must first understand the prevalence in healthy community-dwelling individuals, identify factors associated with ESBL Ent colonization, and determine the significance of environmental surface contamination in the spread of these pathogens. The knowledge gained through the proposed investigations can inform novel infection prevention strategies for decreasing the burden of ESBL Ent in the community. Investigations such as ours that lead to preventive advances will benefit a large number of patients and have a positive impact on healthcare utilization and expenditures. This research will characterize key household ESBL Ent reservoirs and yield valuable insight into potential routes of ARG acquisition and transmission pathways, informing subsequent investigations and targeted interventions.