Abstract Project 1: Epidemiology of MDRO Carriage and Adverse Health Outcomes in Nursing Homes Multidrug-resistant organisms (MDROs) are serious and urgent threats to human health. Although extensive efforts have begun to reverse the tide in hospitals, investments are severely lacking in nursing homes (NHs) where MDRO prevalence is much greater (routinely 65% vs. 10% in hospitals). NHs are unique settings that may be particularly prone to spreading contagion due to their long lengths-of-stay, care of medically vulnerable residents, encouragement of shared spaces and activities, high staff turnover, and limited infection prevention training. Due to scarce resources for screening, surveillance, and strategies to combat MDROs, evidence is needed to create guidelines for MDRO reduction strategies specific to NHs. This project will encompass an in-depth and simultaneous assessment of five major MDROs of clinical significance to the 1.4 million people who are cared for in 15,000 U.S. nursing homes each year. These MDROs include three endemic pathogens that are entrenched in NHs, namely methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and extended-spectrum beta- lactamase producers (ESBLs), as well as two emerging MDROs– carbapenem-resistant Enterobacterales (CRE), and Candida auris, an antibiotic-resistant fungus capable of substantial morbidity and mortality. The goal of the simultaneous assessment of these MDROs is to assess synergistic capture from screening cultures and inform interventions that would target MDROs in concert. We will capitalize on the combination of retrospective and prospective studies involving over 10,000 NH residents from 50 NHs to evaluate efficient ways to sample body sites and environmental objects for MDRO carriage and co-carriage. We also will perform comprehensive assessments of resident, NH, and community- level risk factors for carriage of MDROs, alone and in combination. Beyond carriage, we will use these data to assess risk factors for later MDRO infection and hospitalization. Importantly, we will specifically evaluate whether risk factors are differentially affected by race, ethnicity, and socioeconomic status to better elucidate NH disparities in care delivery or health outcomes. Knowledge of major drivers of carriage and infection will inform the need and value of NH interventions to transform policy and practice.