Project Summary Healthcare-associated infections (HAIs) and antimicrobial resistance (AR) lead to adverse patient outcomes, including increased mortality, morbidity, and length of hospitalization. While progress in prevention is occurring, innovative and improved strategies for prevention of HAIs, AR, and patient harm are needed. The overall objective of this proposal is to identify potential strategies to decrease HAIs and prevent AR emergence, transmission, and acquisition. Our Core Proposal includes 6 unique studies to address 4 specific lines of investigation (specific aims [SA]): environmental disinfection, antimicrobial stewardship, diagnostic stewardship, and community-acquired Clostridioides difficile infection (CA-CDI). These studies will 1) evaluate novel strategies to decrease environmental contamination with opportunistic premise plumbing pathogens related to hospital sinks using a) Pall filters and drain covers (SA1A) and b) engineered plasmids (SA1B); 2) identify and evaluate innovative antimicrobial stewardship (AS) interventions and metrics to decrease AR and patient harm a) at transitions of care (e.g., discharge) in community hospitals (SA2A) and b) related to post-operative antibiotics (SA2B); 3) develop and validate reflex urine culture criteria to guide improved utilization of urine cultures (SA3); and 4) evaluate and determine the contribution of environmental sources on acquisition and occurrence of CA-CDI (SA4). These studies involve patients admitted to community and academic hospitals as well as patients in the community setting. We will achieve this objective by using the strengths of a unique, innovative, and previously successful collaboration between investigators in the Duke Center for Antimicrobial Stewardship and Infection Prevention and the University of North Carolina at Chapel Hill. We will capitalize on programmatic strengths in both institutions: expertise in environmental disinfection, antimicrobial stewardship, infection prevention, AR, epidemiology, surveillance, and emerging infections; access to large and unique research networks and infrastructure; and proven success with collaborative research involving multiple institutions. All Core Projects proposed in this application represent early stage translational research (T0-T1) with clearly identified “next steps” that will help expedite identification and development of practices that effectively prevent HAIs and AR. In addition, we are proposing 3 Collaborative Projects with other CDC Prevention Epicenters Programs: 1) a cluster randomized non-inferiority crossover trial on the use of contact precautions for MRSA and VRE acquisition (Large); 2) evaluation of the feasibility and utility of robust antibiotic use risk-adjustment machine learning models (Medium); and 3) metagenomic evaluation to determine if and how often endogenous flora contaminate surgical wounds (Small). These studies involve patients admitted to community and academic hospitals. Overall...