Project Summary Healthcare-associated infections (HAIs) and antibiotic resistance (AR) are leading causes of morbidity and mortality worldwide. Concerted efforts are required to define the epidemiology and impact of emerging HAI and AR issues, as well as identify and test novel strategies to address these urgent problems. The CDC Prevention Epicenter site at the University of Pennsylvania and the Children’s Hospital of Philadelphia (i.e., the Penn- CHOP Epicenter) has been engaged in numerous initiatives focused on HAIs and AR. The considerable research support and infrastructure provided by the CDC’s Prevention Epicenters Program has served to facilitate significant scientific achievements demonstrated in part by 71 peer-reviewed publications and 110 scientific abstracts from the Penn-CHOP Epicenter group since site inception in 2011. The Penn-CHOP Epicenter has also provided a rich scientific environment within which investigators with complementary areas of expertise collaborate to address the most urgent issues in HAI and AR. Finally, the Penn-CHOP group has collaborated extensively with other CDC Epicenter sites and healthcare networks to answer critical scientific questions. The projects proposed in this application build on the strong foundation established by prior work from the Penn-CHOP investigators. These studies focus on acute, post-acute, and outpatient care settings and include adult and pediatric populations. Finally, these projects include collaborations with other sites, health care networks, public health agencies, and regional partnerships. This application is comprised of 6 Core Projects and 3 Optional Collaborative Projects: CORE PROJECTS Core Project #1: Screening and Targeted Prophylaxis for Clostridioides difficile Infection (CDI) among Immunocompromised Hosts (SToP-CDI) Core Project #2: Non-residential Exposures to Multidrug-Resistant Organisms (NEXUS) Core Project #3: Reducing Antimicrobial Prescribing in Dialysis (RAPID) Core Project #4: Microbiome Sampling in Pediatric Post-Acute Care to Understand Multidrug-resistant Organism Risk, Antibiotic Effect, and Ventilator-associated Infection (MS PAC-MAN) Core Project #5: Natural Language Processing for Antibiotic Prescribing in Sinusitis (NAPS) Core Project #6: Antibiotic Stewardship for Ambulatory Surgery Prophylaxis (ASSURE) OPTIONAL COLLABORATIVE PROJECTS Small Collaborative Project: Communication And Coaching To Increase Steward Influence (CACTIS) Medium Collaborative Project: Reducing Vancomycin Administration in Pediatric Sepsis (REVAMP-Sepsis) Large Collaborative Project: Fecal Microbiota Transplantation to Address Colonization and Environmental Contamination with Multidrug-Resistant Organisms (FACE-MDRO)