Comparative evaluation of metagenomic and targeted next-generation sequencing for pathogen detection in bronchoalveolar lavage fluid from patients with lower respiratory tract infections: a retrospective cohort study
In brief
Metagenomic sequencing reached 91% sensitivity; targeted results changed therapy in 23%
In this retrospective study of 941 patients, metagenomic sequencing had 91% sensitivity versus 73% for targeted sequencing, while targeted tests identified difficult-to-detect pathogens and prompted treatment escalation in 23% of positive cases. About two-thirds of patients improved after escalation, similar to those given appropriate initial therapy, but the study cannot establish whether sequencing improves survival.
- Journal
- Frontiers in cellular and infection microbiology (Q1)
- Published
- 14 October 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Rui Zhao, Heya Na, Wei Miao, Lei Liu, Jing Zhang, Yongshuai Miao, et al.
- PMID
- 42952990
- DOI
- 10.3389/fcimb.2026.1877320
Why clinicians should know about it
- Picked for Microbiology (medical) (paper of the day, 30 October 2026): Direct comparison of sequencing platforms for respiratory pathogen detection
Abstract
BACKGROUND: Rapid and precise pathogen identification is crucial for managing lower respiratory tract infections (LRTIs). While metagenomic next-generation sequencing (mNGS) and targeted next-generation sequencing (tNGS) are emerging as valuable diagnostic tools, large-scale studies directly evaluating their real-world impact on antimicrobial stewardship remain scarce. METHODS: We conducted a retrospective cohort study encompassing 941 patients with suspected LRTIs who underwent bronchoalveolar lavage fluid (BALF) sequencing. Patients were evaluated in either an mNGS cohort (n = 479; DNA-only sequencing) or a tNGS cohort (n = 462; DNA and RNA sequencing). Diagnostic performance, pathogen spectrum, and clinical utility were compared against a composite final clinical diagnosis, which served as the reference standard. RESULTS: Both sequencing platforms demonstrated diagnostic efficacy superior to traditional laboratory tests. In the tNGS cohort, polymicrobial infections were highly prevalent (93.5%). Furthermore, tNGS demonstrated high sensitivity for fastidious pathogens, identifying 54 cases of Mycobacterium tuberculosis (a cohort in which routine smears missed 77.8% of cases) and effectively detecting Pneumocystis jirovecii. The overall diagnostic sensitivity was 90.6% (95% CI: 87.5-93.1%) for mNGS and 73.4% (95% CI:69.2%-77.3%) for tNGS. Guided by tNGS results, clinicians escalated antimicrobial therapy in 22.6% of positive cases. The clinical improvement rate following this targeted escalation was 66.2%, comparable to the 66.7% improvement rate observed in patients receiving appropriate initial empirical therapy (P = 0.946). CONCLUSION: Both tNGS and mNGS offer substantial diagnostic value for LRTIs, with tNGS showing particular utility in identifying fastidious and low-titer pathogens. Sequencing-guided diagnostics frequently informed antimicrobial adjustments and were associated with favorable clinical progress; however, future prospective paired-testing studies are required to isolate the direct impact of sequencing on patient survival outcomes.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.