Project Summary In the U.S. over 150,000 patients die annually from multidrug-resistant infections, and resistant infections are associated with over $20 billion in healthcare costs. Healthcare-associated infections (HAI) highlight the impact of antibiotic resistance, as more than 40% of HAIs are due to antibiotic-resistant organisms. Children requiring mechanical ventilation are at risk for developing ventilator-associated infections (VAI). VAIs are responsible for 23-53% of all HAIs among children. Up to 87% of pediatric intensive care unit (PICU) patients are treated with antibiotics and treatment for suspected VAIs accounts for 50% of antibiotic use in the PICU. In an effort to inform the diagnosis of VAIs, clinicians often obtain respiratory cultures from mechanically ventilated patients. However, these cultures are obtained from a non-sterile site and more than 50% of endotracheal cultures will grow a potentially pathogenic organism within 3 days of intubation regardless of clinical symptoms. Respiratory cultures cannot distinguish between bacterial colonization and infection, and despite the low specificity to indicate infection, positive cultures prompt clinicians to treat with antibiotics. Safely reducing testing, referred to as diagnostic stewardship, is an emerging strategy to reduce testing overuse and potentially antibiotic overuse. Recently, a novel clinical practice guideline designed at the Johns Hopkins Children’s Center to standardize approach to respiratory cultures in critically ill children safely reduced respiratory culture use by 41%. The long- term objective of this proposal is to develop a customizable diagnostic stewardship program that can improve antibiotic use and prevent antibiotic resistance among vulnerable children. The specific aims are Aim 1) evaluate whether diagnostic stewardship of respiratory cultures among mechanically ventilated children decreases respiratory culture use and antibiotic use without leading to unintended patient harm, Aim 2) identify barriers and facilitators to implementation of diagnostic stewardship quality improvement programs to reduce respiratory culture use among mechanically ventilated patients in 14 pediatric intensive care units, and Aim 3) use a Delphi method, including a panel with nationwide representation, to develop consensus recommendations informing when to obtain respiratory cultures in mechanically ventilated children. Fourteen hospitals participating in a multicenter quality improvement initiative, the Bright STAR Collaborative, are implementing local quality improvement programs to improve respiratory culture use. This proposal will evaluate the implementation of local diagnostic stewardship programs and determine whether these programs represent an effective and safe strategy to reduce antibiotic use in a vulnerable population. The proposed aims will assemble the tools and evidence to broadly disseminate diagnostic stewardship as a strategy to reduce antibiotic use and ...