Next-generation sequencing (NGS) can improve pathogen detection in lower respiratory tract infections and help clinicians adjust antimicrobial treatment, according to a study published in Frontiers in Cellular and Infection Microbiology.
Researchers at Chifeng Municipal Hospital, China, retrospectively analyzed 941 patients with suspected lower respiratory tract infections who underwent sequencing of bronchoalveolar lavage fluid between 2021 and 2023.
The study compared two approaches: metagenomic NGS, which broadly screens for microbial DNA, and targeted NGS, which uses a predefined panel to detect specific pathogens.
Both approaches demonstrated greater diagnostic yield than conventional microbiological testing. Overall sensitivity was higher for metagenomic NGS (90.6 percent) than targeted NGS (73.4 percent), although the two methods were evaluated in separate patient groups.
Targeted sequencing showed particular value in identifying difficult-to-detect organisms. It identified 54 cases of Mycobacterium tuberculosis infection, 42 of which were missed by conventional testing. It also detected Pneumocystis jirovecii in cases where routine silver staining produced negative results.
The findings highlight the potential of targeted sequencing to improve detection of pathogens present at low concentrations, which may be overlooked by conventional methods.
Sequencing results also influenced treatment decisions. Among patients with positive targeted NGS results, 22.6 percent required escalation of their initial antimicrobial therapy after sequencing identified pathogens that were inadequately covered by existing treatment.
Following these adjustments, 66.2 percent showed clinical improvement. This was comparable to 66.7 percent of patients whose initial treatment was considered appropriate.
However, both sequencing approaches showed low specificity, highlighting the challenge of distinguishing infection-causing organisms from harmless microbes colonizing the respiratory tract.
The researchers also acknowledged important limitations. The retrospective, single-center study did not test both methods in the same patients, while differences in sequencing protocols complicated direct comparisons. Furthermore, the observed improvements could not be attributed conclusively to sequencing-guided treatment.
Nevertheless, the findings support the potential role of NGS alongside conventional microbiology in diagnosing complex respiratory infections and informing antimicrobial stewardship. Prospective studies are needed to establish whether these diagnostic advantages translate into improved long-term patient outcomes.
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