Associations of targeted next-generation sequencing with antimicrobial stewardship and clinical outcomes in pediatric lower respiratory tract infections

Abstract Background The impact of targeted next-generation sequencing (tNGS) in pediatric lower respiratory tract infections (LRTI) remains largely unknown. We aimed to investigate whether adding tNGS to standard conventional microbiological tests (CMTs), compared with CMTs alone, was associated with antimicrobial stewardship and clinical outcomes. Methods This retrospective cohort study was conducted at Tongji Hospital, Wuhan, between 2023-2024. Pediatric patients hospitalized with LRTI were categorized into tNGS (tNGS in addition to CMTs, typically as a second-line test) or control (CMTs alone) groups based on testing received during the first 4 days after admission. To address potential baseline confounding, we performed 1:2 propensity score matching to balance key clinical characteristics between groups. The primary outcomes were whether and time to provision of pathogen-directed treatment within 96 hours after the index time. Secondary outcomes included other antimicrobial stewardship measures and clinical outcomes. Between-group outcomes were assessed using generalized linear models to estimate risk differences (RDs, identity link) and odds ratios (ORs, logit link) for binary outcomes, while time-to-event analyses were performed using Fine-Gray subdistribution hazard models to account for competing risk of discharge, with results reported as hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Results After matching, 520 participants were included (182 tNGS group; 338 control group). During follow-up, 75 patients (41.21%) in the tNGS group and 48 (14.20%) in the control group received pathogen-directed treatment, with an absolute RD of 27.01% (95% CI: 18.95%, 35.07%) and an OR of 4.23 (95% CI: 2.78, 6.51). The mean time to treatment was 58.99 hours in the tNGS group vs. 82.95 hours in the control group (mean difference, −23.96 hours; 95% CI: −31.02, −16.90), with a corresponding HR of 3.55 (95% CI: 2.47, 5.09). Patients in the tNGS group also had lower rates of non-pathogen-directed antibiotic use (OR=0.52, 95% CI: 0.33, 0.79). Clinical outcomes were similar between the two groups. Conclusions Use of tNGS as a second-line test was associated with faster and more targeted antimicrobial treatment in pediatric LRTIs, but its impact on clinical outcomes requires further investigation. Clinical trial number Not applicable