PROJECT SUMMARY Background: Antibiotics have revolutionized healthcare allowing clinicians the ability to treat life-threatening infections and to prevent infections following life-saving surgery. Unfortunately, antibiotic overuse results in antibiotic resistant bacteria and unnecessary adverse events including Clostridioides difficile infections (CDI). Current data demonstrates that antibiotic resistant bacteria and CDI annually kill up to 150,000 and 29,000 Americans, respectively. Surgical antibiotic prophylaxis is a common area for unnecessary antibiotic use among children. Recent CDC surgical site infection (SSI) guidelines and the AAP Choosing Wisely Campaign recommend no postoperative antibiotic prophylaxis for procedures considered low risk for an SSI. A significant gap exists on the best interventions for antimicrobial stewardship programs (ASPs) and surgeons to de- implement (eliminate) unnecessary postoperative antibiotic prophylaxis in children. Goal: To determine and test two evidence-based implementation strategies to de-implement unnecessary postoperative antibiotic use in children while assessing important clinical outcomes including SSI and CDI. Methods: First, we will develop evidence-based de-implementation strategies guided by the i-PARIHS framework (Integrated Framework for Promoting Action on Research Implementation in Health Services). Based on preliminary data from surgeon focus groups and current literature, standard order set review and modification (control intervention) will be implemented in 9 Children's hospitals that are members of both the SHaring Antimicrobial Reports for Pediatric Stewardship (SHARPS) and the National Surgical Quality Improvement Program-Pediatric (NSQIP-P). Utilizing the iPARIHS framework to understand the key factors involved with implementation, an enhanced ASP facilitation intervention will then be implemented. We will study the impact of these interventions utilizing a stepped-wedge design that will sequentially deliver the facilitation intervention over time to all hospitals. These interventions will be implemented and implementation outcomes (e.g. penetration) will be assessed utilizing established ASPs from the SHARPS collaborative, a large national collaborative dedicated to improving antibiotics in children. Clinical outcomes (e.g. postoperative antibiotic use, SSI, CDI) will be assessed using data collected at each hospital by NSQIP-P. Innovation and Impact: This study is innovative and impactful because it will: 1) combine expertise from surgeons, antimicrobial stewards and implementation scientist to develop theory based strategies to improve antibiotic use; 2) assess the impact of these strategies on surgeries in children, an underrepresented group; 3) rigorously test two interventions utilizing a stepped-wedge design; 4) collect clinical outcomes (e.g. antibiotic use, SSI, CDI) important to ASPs and surgeons; 5) collect implementation outcomes that will inform the dissemination of the strategies to other hospitals; and 6) synergy between 2 large collaboratives (SHARPS & NSQIP) that will enhance pediatric ASPs and improve the care of children requiring surgical procedures.