Abstract Project 2: Evaluating MDRO Transmission Patterns in Nursing Homes Using Pathogen Genomic Data MDRO infections are a major cause of morbidity and mortality for residents in nursing homes (NHs), and these facilities are increasingly recognized as hubs for the rise and spread of MDROs into hospitals and the wider community. Thus, there is an urgent need to be able to sensitively detect, trace and control transmission of MDROs in NHs to limit their impact on residents and the healthcare ecosystem. Despite this need, MDRO dynamics are poorly characterized in this setting. Risk factors for MDRO carriage may not correspond to drivers of MDRO transmission. High pathogen prevalence may be fueled by (i) external importation with admission; (ii) environmental reservoirs; or (iii) inter-person transmission, each requiring distinct measures to reduce pathogen burden. It is also likely that transmission dynamics will differ considerably between organisms, and thus certain interventions may have a differential impact on distinct MDROs. Genomic surveillance of MDROs in NHs is thus urgently needed to complement studies of carriage and prevalence by providing insight into the major drivers of spread within facilities. To address this gap, we will assess the roles of human and environmental pathogen reservoirs contributing to MDRO transmission in nursing homes in order to optimize sampling for genomic surveillance. We will develop integrative models leveraging prospective genomic and epidemiological data from host and environmental sources collected within an optimized multi-modal sampling framework to assess the spread and persistence of MDROs in NHs. Furthermore, we will evaluate commensal organism sharing patterns in NHs using metagenomic sequence data to resolve further microbial transmission networks. As part of a highly integrated framework with the other P01 Projects and Cores, these studies will lead to a more comprehensive view of MDRO transmission patterns in NHs using pathogen genomic data, including a new analytical framework for genomic assessment of endemic pathogen transmission. This work will advance infection prevention and control strategies to detect, trace and eliminate high risk transmission pathways, thus reducing the burden of MDROs in NHs, connected healthcare facilities and the community.