Health system implementation of clinical decision support to optimize respiratory pathogen profile utilization.

Overuse of respiratory pathogen profiles (RPPs) in immunocompetent patients offers limited clinical benefit and may contribute to unnecessary hospital costs. Evidence supports RPP use primarily in severely ill, immunosuppressed, or pediatric patients, while smaller, targeted tests are more appropriate for routine cases . The goal of this study was to evaluate the impact of a clinical decision support (CDS) intervention on RPP utilization and associated reagent costs. We reviewed RPP utilization across the health system and implemented a CDS tool with pre-approved clinical indications to guide appropriate RPP ordering or redirect testing to a smaller seasonal respiratory viral profile (SRVP). Initiation of an RPP order through the CDS tool presented the SRVP as the default, pre-selected option, with users prompted with specific built-in clinical indications before selecting whether to proceed with an RPP or SRVP. Data from inpatient and emergency department settings from January 2022 to January 2026 were used to assess RPP ordering practices pre- and post-CDS implementation. The impact of the CDS implementation on RPP orders was assessed using an interrupted time series analysis. Retrospective analysis revealed a year-to-year increase in RPP orders from 2022 to 2024. After CDS implementation, there was an immediate and significant decrease in RPPs compared to the pre-CDS period (-946.70, 95% CI: -1,320.2 to -573.2). This corresponded to $2.26 million in reagent cost savings. Overall, the introduction of the CDS successfully reduced the overutilization of large respiratory pathogen syndromic panels by encouraging the use of a SRVP when clinically appropriate. IMPORTANCE: Diagnostic stewardship ensures that multiplex molecular assays are used to deliver the right test, for the right patient, at the right time. Through coordinated input from interdisciplinary teams across the diagnostic pathway, stewardship enhances test selection, resource utilization, and interpretation of complex syndromic panels. Although multiplex PCR assays offer high sensitivity, their ability to detect residual nucleic acid from nonviable or colonizing organisms can create diagnostic ambiguity; therefore, it is important to have stewardship frameworks in place to guide appropriate test ordering, timing, and result interpretation and to avoid misinterpreting results. Through integration of laboratory expertise and evidence-based indications, diagnostic stewardship enhances the clinical value of multiplex testing and limits unnecessary treatment and downstream costs.