PROJECT SUMMARY We enthusiastically propose to renew our CDC Prevention Epicenter, entitled “InterMountain Program in Antibiotic Resistance and microbial Threats (IMPART). Our proposal assembles an exceptional group of investigators who have an extraordinary capacity to conduct large-scale observational studies, as well as lead or co-lead interventional studies that range in scope from small pilots to multi-community randomized trials The University of Utah is the hub for our program, with Intermountain Health, a large regional integrated health system, serving as a major node. The Veterans Affairs (VA) Salt Lake City Healthcare System is another key partner for our Prevention Epicenter site, operating within a programmatic network that encompasses the entire VA health system. The resources that we bring to the CDC Prevention Epicenter Program will be broadly beneficial to its mission to improve healthcare safety and prevent healthcare-associated infection. We have accumulated the experience in translational research and expertise in multi-disciplinary methods to make significant contributions to improve the quality of antibiotic use, combat antibiotic resistance, and enhance health system response to microbial threats across the continuum of care. Moreover, we have developed a computational environment to support comprehensive epidemiological analysis of infections within the Department of Veterans Affairs (VA) Health System, as well as Intermountain Healthcare and University of Utah Health (UHealth). Our proposed research has a high level of significance for policy-making and implementation. Core Project 1 evaluates alternative implementation strategies for outpatient stewardship and advances dissemination of best practices for AS. Core Project 2 tackles a longstanding source of controversy in the healthcare epidemiology community, namely, the role of active surveillance and contact precautions (CP) in preventing healthcare-associated infection due to endemic multi-drug resistant organisms (MDRO) such as methicillin-resistant Staphylococcus aureus (MRSA). A period of partial CP deimplementation in some VA facilities, triggered in response to the emergence of COVID-19, creates the opportunity to study the impact of this natural experiment. Core Project 3 links an epidemiological analysis of transmission pathways in LTC facilities to the development and implementation of novel approaches to improve practice. Core Project 4 confronts the global health challenge of COVID-19, to enhance preparedness for future epidemics and increase understanding of how to control healthcare spread of both seasonal and novel viruses. We are committed to active engagement with other Prevention Epicenter sites on collaborative projects and to work closely with public health entities at national, state, and local levels. We also pledge to contribute to programmatic domains and pathogen-specific workgroups set up under the auspices of the Prevention Epicenter Program. F...