PROJECT SUMMARY Antimicrobial resistant organisms (ARO) have long been a concern in the acute healthcare setting, but community rates have increased exponentially over the past decade, with the Centers for Disease Control and Prevention (CDC) estimating that 47% of all extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) infections are now community-associated (CA). Despite this, very little is known about community- associated AROS (CA-ARO). The goals of this proposal are to characterize AROs in the community setting and to identify risk factors for CA-ARO infection and colonization. Our central hypotheses are that there are identifiable risk factors associated with CA-ARO infection and colonization, and that these data will lay the groundwork for interventions to reduce the transmission of AROs and to ultimately prevent ARO infections. In Aim 1, we will characterize clinical risk factors associated with CA-ARO infections utilizing a database of patients with urinary tract infections and bloodstream infections associated with both community and healthcare settings. In Aim 2 we will determine the prevalence and clinical risk factors associated with CA-ARO colonization in patients admitted to the acute care hospital setting. This will be achieved through recruiting patients admitted to the hospital from the community setting and interrogating clinical specimens with selective microbiologic culture to determine the prevalence of ARO colonization and identify risk factors for CA-ARO colonization in this population. In Aim 3 we will determine the prevalence and characteristics associated with ARO colonization in asymptomatic community volunteers and their home environment to identify risk factors and reservoirs of CA-ARO colonization. We will achieve this through a prospective cohort study of community volunteers and interrogation of human and environmental samples paired with detailed clinical data to document reservoirs of CA-ARO and potential risk factors for CA-ARO colonization. Together, this data will provide key insight to understand CA-AROs, a necessary first step towards creating interventions to combat AROs in community settings. Results of this study will directly impact clinical practice by providing key data to guide the use of infection prevention interventions for people at-risk for CA-ARO colonization or infection, environmental hygiene recommendations, and empiric antimicrobial use in the community setting. This study is directly responsive to the AHRQ FOA focused on the prevention of HAIs as it is aimed at reducing the transmission of AROs and preventing HAIs. This project represents a necessary and novel approach to targeting AROs within the community setting, and will lead to practice-changing paradigms to combatting AROs.