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.
