To assess the diagnostic performance of metagenomic and targeted next-generation sequencing (NGS) of bronchoalveolar lavage fluid in patients with suspected lower respiratory tract infections, and examine how sequencing results affected treatment.
Approach:
Study design: Researchers at Chifeng Municipal Hospital retrospectively analyzed 941 patients tested between 2021 and 2023.
Methods compared: Metagenomic NGS broadly screened for microbial DNA; targeted NGS tested for pathogens on a predefined panel. Results were compared with conventional microbiological testing.
Key Findings:
Both NGS approaches had greater diagnostic yield than conventional microbiological testing. Reported sensitivity was 90.6% for metagenomic NGS and 73.4% for targeted NGS; the methods were assessed in separate patient groups.
Targeted NGS identified 54 cases of Mycobacterium tuberculosis, including 42 missed by conventional testing, and detected Pneumocystis jirovecii in cases with negative routine silver staining.
Among patients with positive targeted NGS results, 22.6% had antimicrobial therapy escalated after sequencing identified pathogens inadequately covered by initial treatment.
Clinical improvement was reported in 66.2% of patients whose treatment was adjusted, compared with 66.7% of patients whose initial treatment was considered appropriate.
Both sequencing approaches had low specificity, limiting their ability to distinguish infection-causing organisms from respiratory tract colonization.
Interpretation:
The study authors report that NGS may complement conventional microbiology in diagnosing complex respiratory infections and informing antimicrobial treatment. The study did not establish that sequencing-guided treatment caused the observed clinical outcomes.
Limitations:
Retrospective, single-center study.
The two sequencing approaches were not tested in the same patients.
Differences in sequencing protocols complicated direct comparisons.
Improvements could not be conclusively attributed to sequencing-guided treatment.
Conclusion:
The authors call for prospective studies to determine whether NGS diagnostic advantages translate into improved long-term patient outcomes.
