Core Project Summary The Chicago Prevention and Intervention Epicenter will focus on objectives promoted by CDC. Through our core projects we will make epidemiologic and basic science discoveries and technological innovations translatable into strategies to prevent spread of antimicrobial-resistant organisms within facilities and regionally across the web of interconnected facilities. To control endemic antimicrobial-resistant pathogens, and to mitigate emerging, novel mechanisms of resistance, a bundle of interventions is needed and applied across the spectrum of healthcare facilities. We propose an ambitious portfolio of projects in hospitals, long-term acute care hospitals (LTACHs), and skilled nursing facilities. Our projects span the infection control domains of interest to CDC, annotated by the following six core projects (abridged for this summary): Project 1: Predictive modeling to identify patients at high-risk for MDROs to inform Illinois' XDRO registry. Population, hospital and LTACH patients. Domain, regional control including long-term care facilities. Project 2: Regional active MDRO surveillance with genomic analysis. Population, hospitals, LTACHs and nursing homes. Domain, containment of novel resistance. Project 3: Geospatial, ecologic, and clinical risk factors for community-associated ESBL-producers. Population, emergency department and ambulatory patients of two large, urban health systems. Domain, community-associated antimicrobial-resistant infections. Project 4: Genomic epidemiology of MDRO transmission in ICUs. Population, hospital ICU patients. Domain, applying innovative research methodology to evaluate MDRO transmission. Project 5: Adverse health outcomes associated with microbiota disruption. Population, medical ICU patients. Domains, effects of antibiotic use and diagnostics—evaluating measures of the microbiome. Project 6: Generate and export reports on antimicrobial use metrics from a national common data model. Population, hospital patients. Domain, Antimicrobial stewardship