Our proposed research addresses healthcare-associated infections caused by multidrug-resistant organisms (MDROs) across the healthcare spectrum from pre-hospital arena, into acute short-term though long-term care facilities. We have capacity to engage in research activities at the largest healthcare system in the Atlanta metropolitan area using Emory’s Clinical Data Warehouse, established research ties to a multi-state network of nursing homes, and long-standing research collaborations with other Prevention Epicenters, the Georgia Emerging Infections Program and Georgia Department of Health. PEACH investigators have national recognition in MDROs and have contributed to the Prevention Epicenters mission in the past. PEACH II will be advancing transdisciplinary research incorporating human factors engineering, microbiome and environmental ecology, and informatics into transmission interruption efforts, in a diverse spectrum of settings. We propose to advance the Prevention Epicenter’s research mission through (1) engagement with a broad range of Emory and partner institute scientists with expertise to contribute to Epicenter work, (2) collaborative observational and clinical trials including study conduct, data use agreements, ethics approvals, and laboratory practices by leveraging access to diverse (including underserved) patient populations across the healthcare spectrum, and (3) expand collaborations with other Prevention Epicenters and Emerging Infections Programs sites. Towards this latter aim, we are proposing four Core Projects: Core Project 1: InPART Rx - Inpatient Provider Antibiotic Rate Benchmarking to Reduce Unnecessary Prescribing; T1: in Acute Care settings, Priority Areas of Stewardship, decreasing AR infections; Core Project 2: FAIR – A clinical trial of Fecal Microbiota Transplant for Antibiotic-Resistant Infections in Inpatients; T1 – in Acute Care settings, Priority Areas: Decreasing AR infections, Understanding and decreasing transmission (source control, environment), Regional control, Epidemiologically important pathogens in healthcare, Asymptomatic colonization, and Microbiome; CORE PROJECT 3: PRE-ALERT - Predicting Admissions Likely Colonized with Antibiotic Resistant Bacteria to Trigger Detection and Isolation; T-1: Acute care and Post-acute care, Priority Areas of Regional control of AR; Innovative detect and response; Core Project 4: CHAMPIONS – Collaborative Human Factors and Microbiology Approaches to Prevent Infections in Post-acute Care; T1: in Long-Term Care, Priority Areas: Decreasing AR infections. Understanding and decreasing transmission- environment; Regional control and long-term care facilities. Additional optional collaborative projects target innovations around hand hygiene effectiveness multiple acute care settings, containment of emergence resistance in long term acute care and nursing homes and improving sepsis management in multiple pre-hospital settings.