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.

项目总结