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.

Clinical progress note: Update in management in community acquired pneumonia in children

“…6 A large meta-analysis of adults hospitalized with pneumonia found a high negative predictive value using methicillinresistant S. aureus nasal screens, indicating that nasal screen can be useful to rule out S. aureus pneumonia; there are minimal studies on the utility of such screening in children. 7 Antibiotics should be transitioned to oral as soon as a child demonstrates clinical improvement, even in cases of CAP complicated by bacteremia. In most cases, prolonged outpatient parenteral therapy is not warranted.…”

“…Recommended empiric therapy is with a third‐generation cephalosporin; anti‐staphylococcal therapy is recommended for children with severe or rapidly progressive disease, extensive local complications, or poor treatment response after 48–72 h of therapy 6 . A large meta‐analysis of adults hospitalized with pneumonia found a high negative predictive value using methicillin‐resistant S. aureus nasal screens, indicating that nasal screen can be useful to rule out S. aureus pneumonia; there are minimal studies on the utility of such screening in children 7 …”

Clinical progress note: Multiplex panels for identifying infection in children

“…This limitation can be addressed by using metagenomics, which offer a nondirected, comprehensive evaluation of microbial genetic material with the tradeoff of extending turn‐around‐time (TAT) 2 . Metagenomic testing in children admitted to the general ward with complicated community‐acquired pneumonia increased the diagnostic yield from 26% in conventional testing (blood and respiratory cultures and viral PCR) to 89%, in conventional testing, contributing to management changes in 78% of cases 5 . Additionally, metagenomic testing may have utility in diagnosing infections in immunocompromised persons, it detected blood stream infections up to 3 days before onset of clinical symptoms 6 .…”

The Notable Achievements and the Prospects of Bacterial Pathogen Genomics

“…A number of complex bioinformatics pipelines are currently being applied and developed to analyse such challenging data (for comprehensive reviews see [ 116 , 117 ]). Cell-free plasma Next-Generation Sequencing (cfNGS), a form of plasma metagenomics, is already being adopted with success in certain clinical settings such as paediatric complicated pneumonia [ 118 ].…”