# Clinical impact of targeted next-generation sequencing in paediatric pneumonia management: a real-world study evaluating diagnostic concordance and antimicrobial stewardship across multiple specimen types

## TL;DR

This study shows that targeted next-generation sequencing detects more pathogens in children with pneumonia than traditional methods and changes antibiotic use in a third of cases.

## Contribution

The study demonstrates tNGS's superior pathogen detection and its impact on antimicrobial stewardship in pediatric pneumonia.

## Key findings

- tNGS detected pathogens in 96.9% of cases compared to much lower rates with conventional methods.
- tNGS results led to antimicrobial changes in 30.2% of patients, mostly de-escalations.
- Age was the only significant predictor of therapy changes based on tNGS results.

## Abstract

This study aims to evaluate the clinical utility of targeted next-generation sequencing (tNGS) in a real-world paediatric pneumonia cohort.

A retrospective cohort study was conducted of 586 children hospitalised with pneumonia who underwent tNGS testing alongside conventional microbiological methods. The study evaluated diagnostic concordance between tNGS and composite reference standards, assessed the impact on antimicrobial therapy changes within 48 h and identified predictors of tNGS-guided therapy modifications. Statistical analyses included McNemar’s test for paired comparisons, Cohen’s kappa for concordance and multivariable logistic regression for predictors of therapy change.

Among the 586 patients (median age 5.0 years, 48.5% girls), tNGS showed a significantly higher positivity rate of 96.9% compared with 45.2% for polymerase chain reaction (PCR; 13 respiratory pathogens panel), 38.1% for culture, 15.4% for antigen testing (influenza A/B, respiratory syncytial virus, adenovirus, Mycoplasma pneumoniae) and 25.3% for serology (all P < 0.001). The diagnostic concordance between tNGS and composite reference standards showed high positive percent agreement (97.4%, 95% confidence interval [CI] 95.7%–98.5%) but low negative percent agreement (6.0%, 95% CI 2.0%–13.5%), with poor overall concordance (κ = 0.05, 95% CI 0.01–0.09). Targeted NGS results led to antimicrobial therapy changes in 30.2% of patients (95% CI 26.5%–33.9%), with 61 escalations, 72 de-escalations and 44 class switches. Age was the only significant predictor of therapy change (adjusted odds ratio 1.14, 95% CI 1.08–1.20, P < 0.001). Specimen-type analysis revealed the highest culture positivity in bronchoalveolar lavage (56.7%) and the highest PCR positivity in sputum (69.2%).

Targeted NGS showed higher pathogen detection rates than conventional methods and influenced antimicrobial management in nearly one-third of paediatric pneumonia cases. The predominance of de-escalation suggests potential for antimicrobial stewardship. However, the low negative percent agreement indicates that tNGS may detect clinically insignificant organisms.