Healthcare-associated infections (HAIs) result in substantial morbidity and mortality and add to the rising cost of health care. HAIs are increasingly caused by antibiotic-resistant bacteria. Among the most serious HAI threats are carbapenem-resistant Enterobacteriaceae (CRE) and Clostridium difficile (C. difficile). Our project addresses this significant public health problem and establishes a consortium of experts in infectious disease modeling, HAI prevention, and public health practice. RTI International, UNC Health Care, and the North Carolina Department of Health and Human Services (NC DHHS) will partner to create the North Carolina Modeling Infectious Diseases Network (NC MIND). Via NC MIND, we will conduct innovative research to realize these specific aims: (1) Build, calibrate, and validate an agent-based simulation model (ABM) of an NC regional healthcare network (HNET) and extend it to a statewide platform. We will adapt RTI's simulated population and develop an ABM of an NC regional healthcare network, extend the ABM statewide, and use the ABM to assess the impact of HAI prevention interventions. The simulated NC population provides an accurate representation of the populations' s sociodemographic attributes and locations, including households, hospitals, and long-term care facilities; (2) Link patient movement to high-risk areas for CRE and C. difficile infection within HNET, creating an NC regional healthcare network infectious disease model (HNET-ID). We will extend HNET to HNET-ID by determining the areas within a healthcare network that pose a high-risk for HAIs and developing methods that associate the probability of CRE or C. difficile infection with patient traits, hospital characteristics, and the natural history of the pathogen. We will use HNET-ID to conduct simulated epidemiologic studies of HAI prevention interventions, such as active surveillance for colonization at hospital admission and subsequent isolation of colonized patients; and (3) Assess the utility of HNET-ID in public health practice and use results to inform policy. We will conduct a demonstration project with NC DHHS to evaluate the utility of the tools we develop. We will disseminate our findings and results to public health and healthcare stakeholders through presentations and manuscripts that inform and influence public health policy. Successful completion of our project aims will build capacity for preventing CRE, C. difficile, and other emerging HAI threats by increasing understanding of the transmission dynamics of HAIs, evaluating HAI prevention interventions, developing computational tools to better understand HAI spread, and informing practices for risk identification and implementation of public health prevention and control measures.