Abstract Corresponding Author Gustavo R. Alvira-Arill, PharmD, Department of Clinical Pharmacy Victoria Isgett, no conflict; Morgan Franklin Wright, no conflict; Stephen A. Thacker, no conflict. Background Plasma metagenomic next-generation sequencing (mNGS) is a new molecular diagnostic tool used to detect microbial cell-free DNA in patients with deep-seated and difficult-to-diagnose infections. The Karius Test is a commercially available plasma mNGS assay with increasing utilization in pediatric hospitals. However, the impact of results from this assay on antimicrobial therapy modifications in pediatric patients remains unclear. Given potential costs associated with testing, the purpose of this study was to assess the clinical impact of Karius Test results on antimicrobial therapy modifications for inpatient pediatric patients being managed for systemic infections. Methods A retrospective review of pediatric patients who underwent Karius testing from January 2024 to September 2024 was performed. Test results were reviewed for impact, defined by modifications to antimicrobial therapy following receipt of results or correspondence with infection. Modifications performed were categorized as de-escalation, defined as modifications resulting in more narrow-spectrum coverage; escalation, defined as modifications resulting in more broad-spectrum coverage; or discontinuation of therapy. Conventional microbiologic testing was also recorded with respect to timing and results of Karius testing. Immune status was recorded as a patient-specific factor. Test-specific factors recorded include primary service team, active infectious diseases consultation, and indication for testing. Results A total of 57 Karius Test results were reviewed from 44 patients during the study period. Most patients were immunocompetent (18/44 40.1%), but a notable proportion were immunocompromised by leukemia (10/44 22.7%), solid organ transplant (5/44 11.4%), or other cancer (5/44 11.4%). The indication for testing varied and included fever of unknown origin (22/57 38.6%), bloodstream/endovascular infections (10/57 17.5%), respiratory tract infections (9/57 15.8%), and febrile neutropenia (8/57 14%). Most tests were performed by a hematology/oncology primary team (30/57 52.6%) and infectious diseases services were involved before performing the test (30/57 52.6%). Of the 57 tests performed, 32 (56.1%) were positive and 24 (42.1%) were determined to be clinically impactful. Antimicrobial therapy modifications were performed based on the results of 13/57 (22.8%) tests, which included de-escalation (6/13 46.1%), escalation (3/13 23.1%), and discontinuation of therapy (4/13 30.8%). Modifications were more likely to occur when Karius Test results were available prior to conventional microbiologic testing (8/13 61.5%). Conclusion Given the limited number of antimicrobial therapy modifications, the impact of Karius Test results for management of systemic infections in pediatric patients remains unclear. However, the impact of testing is likely confounded by timing and comparison to conventional microbiologic testing results. The cost and variability in impact on clinical management and outcomes highlights the need for structured guidance on use and interpretation.
Alvira‐Arill et al. (Mon,) studied this question.
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