Abstract Project 3: Simulating the Spread and Control of Multiple MDROs Across a Network of Nursing Homes in a Region Multidrug-resistant organisms (MDROs) cause nearly 3 million healthcare-associated infections (HAIs), which are a major cause of death in US nursing homes (NHs), annually. While MDROs are commonly studied in isolation, these pathogens circulate simultaneously, and their spread and prevention may affect and compound each other. Therefore, determining the value of such strategies in NHs requires an understanding of how they would affect colonization and infection risks of various MDROs simultaneously. Moreover, the impact of MDROs and their prevention and control strategies extend beyond individual NHs and involve the dynamic ecosystem of NHs in a region. Computational modeling that integrates epidemiologic, operational, and economic components can help delineate the circulation and impact of multiple MDROs, test various prevention and control strategies, and determine the subsequent ecosystem-wide effects related to transmission and disease burden in ways that can save time, effort, and resources. The overall goal of this proposed project is to elucidate (1) the combined effects of multiple MDROs spreading simultaneously and (2) how policies and interventions (e.g., contact precautions, decolonization) may have an impact across a variety of MDROs at the same time, using agent-based models (ABMs) of NHs in Orange County (OC), California (CA). These detailed representations of NHs will include and help differentiate among various multi-level factors affecting MDRO spread. This modeling Project will proceed in a synergistic, iterative manner with the other two Projects. Model results will guide data collection and analyses for Projects 1 and 2, and data insights from Projects 1 and 2 will guide further refinement of the models. Shifting the focus from one MDRO at a time to various MDROs collectively will help decision makers choose the best overall infection control strategy. Specific Aim 1 will develop ABMs for each of the 70 nursing NHs in OC, CA simulating how multiple MDROs (methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, and Candida auris) interact among carriers and co-carriers to promote spread. Specific Aim 2 will evaluate how different pathogens, host factors (e.g., comorbidities, wounds, bedbound status), and room characteristics (e.g., roommates, common areas, shared equipment) simultaneously affect MDRO transmission in NHs across a region using the various NH ABMs. Specific Aim 3 will estimate how various pathogen-specific and non-specific multi-modal strategies may affect the transmission and spread of different MDROs individually and simultaneously in NHs across a region using the NH ABMs.