DESCRIPTION (provided by applicant): The proposed career development award is designed to support the transition of Dr. Adam L. Hersh into an independent physician-scientist using comparative-effectiveness research (CER) methods applied to a patient- centered outcomes research (PCOR) agenda that is dedicated to improving the appropriateness, quality, and safety of antibiotic use of in pediatric care. Dr. Hersh is a pediatric infectious diseases specialist at he University of Utah. The next steps in his career development are to gain advanced skills in quality improvement, epidemiologic, and biostatistical methods for CER and health economics. Dr. Hersh has assembled a mentoring and advisory team with expertise that spans these areas. His AHRQ K08 application proposes 3 research and 4 career development aims that will collectively enable him to become a leader in the areas of antimicrobial stewardship and CER methods in pediatric infectious diseases. Dr. Hersh's application addresses the growing health and economic threat of antibiotic resistance, which is driven in part by the problem of antibiotic overuse. Two important areas of antibiotic overuse include (1) the use of broad-spectrum antibiotics instead of equally effective narrow- spectrum therapy, especially for respiratory infections such as pneumonia; and (2) the use of outpatient parenteral antibiotic therapy (OPAT) instead of equally effective, safer, and less costly oral therapy. The development and implementation of antimicrobial stewardship programs (ASPs) are key strategies to address antibiotic overuse in these areas. However, pediatric ASPs are limited by a weak evidence-base, particularly pertaining to their effectiveness in facilitating guideline uptake and in the comparative-effectiveness of OPAT versus oral therapy for common conditions such as pneumonia, both of which will be strengthened by the proposed research aims. Aim 1 will compare the use of guideline recommended narrow-spectrum antibiotic therapy for pneumonia between hospitals with and without ASPs in a large network of freestanding children's hospitals as a way to assess their effectiveness in facilitating guideline adoption. Aim 2 will compare clinical outcomes between oral therapy and OPAT for children with complicated pneumonia, a condition where treatment practices are highly variable. Finally, Aim 3 will compare the economic burden, including direct and indirect costs and caregiver quality-of-life, between children treated with oral therapy and OPAT in order to provide a better understanding of the economic and caregiver impact of OPAT. In addition to his research aims, Dr. Hersh has proposed four career development aims including coursework and practical experience in the areas of quality improvement; advanced epidemiologic and biostatistical methods for CER; health economics; and leadership. To complete these aims, Dr. Hersh will have access to strong, established resources. The Department of Pediatrics at the University of Utah and Primary Children's Hospital, operated by Intermountain Healthcare, provide ideal environments for the proposed award including a longstanding history and culture of collaborative scientific investigation in the areas of pediatric respiratory infections, quality improvement, implementation science, and CER. The Department of Pediatrics promotes success of early stage investigators by providing resources dedicated to enhancing access to mentorship and grant support services, including a Pediatric Clinical and Translational Research Scholars Program. The University of Utah has outstanding resources dedicated to mentorship, and early career development and training in biostatistical and epidemiologic methods for CER through the NIH-funded Center for Clinical and Translational Science (CCTS) and the Study Design and Biostatistics Center. Intermountain Healthcare offers the Advanced Training Program, a leading training program for physicians in the science of quality improvement. Dr. Hersh currently has 75% protected time which will be ensured throughout the award period to utilize these resources in achieving his career development goals.

PUBLIC HEALTH RELEVANCE: Antibiotic overuse is one of the most common and costly medical errors in pediatric clinical care and directly contributes to the growing health and economic threat of antibiotic-resistant infections. There is an urgent need for better evidence about strategies that effectively reduce antibiotic overuse in pediatrics, including approaches to reducing unnecessary broad-spectrum therapy for respiratory infections and overuse of intravenous therapy in place of oral therapy, both of are rapidly increasing in children. This application uses comparative-effectiveness research methods and engages physicians, patients and families to develop new evidence that will safely reduce antibiotic overuse and its consequences including resistance, treatment-related complications, healthcare costs and caregiver burden.