Impact of Cell-Free Next-Generation Sequencing on Management of Pediatric Complicated Pneumonia

Abstract

BACKGROUND Community-acquired pneumonia (CAP) is common in pediatrics. More severe complicated CAP (cCAP) requires broad-spectrum empirical therapy. Cell-free plasma next-generation sequencing (cfNGS), a DNA-based diagnostic tool, could be used to guide therapy. We retrospectively compared the pathogen identification rate of cfNGS to that of standard culture methods and assessed the impact of cfNGS on antibiotic therapy in children hospitalized for cCAP. METHODS We conducted a retrospective review of children aged 3 months to 18 years hospitalized for cCAP with cfNGS results from January 24, 2018, to December 31, 2020. We compared the positivity rate of conventional microbiologic diagnostic testing with that of cfNGS and the impact on clinical management, including changes in antibiotic therapy. RESULTS We identified 46 hospitalized children with cCAP with cfNGS results. Of these children, 34 also had blood cultures (1 positive for pathogen; 3%) and 37 had pleural fluid cultures (10 positive for pathogen; 27%). Of the 46 children, positive cfNGS testing results were positive for pathogen in 45 (98%), with the causative pathogen identified in 41 (89%). cfNGS was the only method for pathogen identification in 32 children (70%). cfNGS results changed management in 36 (78%) of 46 children, with the antibiotic spectrum narrowed in 29 (81%). CONCLUSIONS cfNGS provided a higher diagnostic yield in our pediatric cCAP cohort compared with conventional diagnostic testing and affected management in 78% of children. Prospective studies are needed to better characterize the clinical outcome, cost-effectiveness, and antimicrobial stewardship benefits of cfNGS in pediatric cCAP.