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

家庭是社区获得性超广谱产β-内酰胺酶肠杆菌的储存库

• 批准号: 10742488
• 负责人: Latania K. Logan
• 金额: $ 25.28万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10742488
• 关键词: Adult; Antibiotic Resistance; Antibiotics; Automobile Driving; Bacterial Antibiotic Resistance; Bacterial Infections; Base Sequence; Biological Specimen Banks; Cessation of life; Chicago; Child; Childhood; Clinical; Communities; Cyclophosphamide; Data; Data Collection; Detection; Ecology; Elements; Environment; Environmental Pollution; Epidemic; Epidemiologic Factors; Epidemiology; Event; Expenditure; Exposure to; Extended-spectrum β-lactamase; Future; Genes; Genetic; Geography; Goals; Healthcare; High Prevalence; Hospitals; Household; Human; Incidence; Individual; Infection; Infection prevention; Interruption; Intervention; Investigation; Knowledge; Length of Stay; Link; Measures; Metadata; Molecular; Multi-Drug Resistance; Outcome; Participant; Pathway interactions; Patients; Persons; Predisposition; Prevalence; Prevention strategy; Preventive; Prospective Studies; Public Health; Reporting; Research; Resistance; Risk; Role; Route; Sample Size; Sampling; Site; Source; Specialist; Specific qualifier value; Surface; Virulent; bacterial resistance; beta-Lactamase; biobank; built environment; candidate identification; clinical candidate; community setting; community transmission; cost; genome sequencing; health care service utilization; health care settings; human data; insight; member; methicillin resistant Staphylococcus aureus; novel; pathogen; prevent; prospective; resistance gene; resistant strain; sample archive; transmission process; whole genome

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.

项目摘要 肠杆菌对多种抗生素具有抗药性，使其成为全球流行病公共卫生 威胁。扩展光谱β-内酰胺酶产生的肠杆菌（ESBL ENT）感染历史上是 仅限于医疗保健环境，但是在过去的二十年中，感染已经大大增加 发生在没有医疗保健接触的情况下健康的儿童和成人中。这些社区的经验 （CA）ESBL ENT菌株在流行病学和遗传上与医疗保健获得的菌株不同，但 类似地与严重感染，高成本，长期住院，随后的医院蔓延以及 结果不佳。重要的是，已经从医疗保健环境中回收了Esbl 人类的传播事件，但家庭环境对社区获得的人类的贡献 感染未知。我们最近发现，在儿童中，Esbl感染的感染量增加了4-34倍 与易感菌株的感染相比，可能是社区的。这似乎是悖论的亮点 传播动力学，储层和抗生素抗性基因来源的关键差距 （args）在ca-esbl ent中。需要此类信息来告知中断社区传播的策略。 拟议的研究将产生有关基于社区的抗性暴露的重要新知识 通过检查健康的人和潜在的家庭环境来源中的马车来检查细菌。提案 有两个目标：1）在健康儿童的家庭中，测量Esbl Ent的患病率和分子生态 环境污染； 2）衡量健康个体中Esbl Ent殖民的患病率 在家庭中，并探索与Esbl Ent的运输相关的个体流行病学因素。一个 在人类和 环境样品将评估可能有助于抗性应变类型的传播的家庭储层。 现在，社区是一个重要且不断扩大的水库，用于扩散有毒的Esbl Ent菌株 医院对临床医生和感染预防专家提出了新的挑战。有效减轻 在医疗保健和社区环境中传播Esbl Ent菌株，我们必须首先了解患病率 在健康的社区居民中，确定与Esbl殖民化相关的因素，并确定 环境表面污染在这些病原体扩散中的重要性。知识 通过拟议的调查获得的可以为新颖的感染预防策略提供信息，以减少 社区中Esbl的负担。导致预防进步的调查将受益 大量患者，对医疗保健利用和支出产生积极影响。这项研究 将表征关键的家庭埃斯特水库，并对ARG的潜在途径产生宝贵的见解 获取和传输途径，告知随后的调查和有针对性的干预措施。