Background: Under-investments in antimicrobial discovery, antimicrobial stewardship, and infection control have reached crisis proportions. While these under-investments have been laid bare by SARS-CoV-2, antimi- crobial-resistant infections—a more silent killer—are accelerating with three million illnesses, 48,000 deaths and $35 billion in excess costs annually in the US, secondary to treatment failure and associated higher morbidity and mortality. The ongoing pandemic of COVID-19, the disease caused by SARS-CoV-2, has also revealed much about the limits of our public health infrastructure and the need to rapidly engage partners, dis- seminate best practices, and adapt to changing conditions during times of widespread uncertainty. Our national, integrated healthcare system for Veterans offers unique opportunities to significantly alter the course of events and improve the outlook for our future through novel implementation and quality improvement efforts. Objectives: The goal of this QUERI program is to continue the successes of its predecessor by addressing the growing concern of antimicrobial resistance and other emerging infectious threats through strategies that train, communicate, and coordinate front-line staff, operational leaders, and field experts. In doing so, we will address the priority goals of our VA operational partners, increase the impact of VA research findings through bi-directional partnerships and rigorous evaluation, and promote VA as a high reliability organization through innovative implementation science. Three projects designed to implement key evidence-based practices in the areas of infection prevention, biosurveillance, and antimicrobial stewardship will target the behaviors and processes that facilitate the spread of antibiotic-resistant and other emerging pathogens, including (1) improv- ing patient safety through overcoming barriers to Ultraviolet-C (UVC) no-touch room disinfection; (2) improving implementation of strategies to prevent the spread of carbapenem-resistant organisms (CROs); and (3) estimating the impact of two different electronic audit and feedback strategies on antimicrobial prescribing practices. These efforts will be supplemented with time-sensitive rapid response projects guided by our operational partners to assist their work with front-line providers across the country. We will also train a new generation of VA implementation scientists through our mentoring core, led by investigators committed to developing junior implementation researchers committed to careers improving the quality, safety, and value of Veteran health care. Methods: The program will employ complementary implementation strategies and theories guided by an Implementation Core consisting of a team of notable VA implementation scientists with proven track records in designing and executing programs to control antimicrobial resistance and prevent the spread of pathogens. We will follow the principles of High Reliability Organizat...