Utilizing Targeted Next-Generation Sequencing for Rapid, Accurate, and Cost-Effective Pathogen Detection in Lower Respiratory Tract Infections.

Objective: To evaluate the diagnostic performance and clinical impact of targeted next-generation sequencing (tNGS) in patients with suspected lower respiratory tract infections. Methods: Following propensity score matching, we compared the diagnostic performances of tNGS and metagenomic next-generation sequencing (mNGS). Furthermore, the diagnostic performance of tNGS was compared with that of culture, and its clinical impact was assessed. Results: After propensity score matching, the coincidence rate of tNGS was comparable to that of mNGS (82.9% vs 73.9%, P=0.079). The detection rates for bacterial, viral, fungal, and mixed infections were not significantly different (P>0.05). Bacterial-viral co-infection (16.7%) was the most common mixed infection detected by tNGS. tNGS showed a higher detection rate than culture (75.2% vs 19.0%, P<0.01). The positive detection rate by tNGS was not significantly different between immunocompromised and immunocompetent patients (88.6% vs 80.5%, P=0.202), but was significantly higher than that by culture (P<0.001). Moreover, 65 patients (44.5%) had their medications modified based on the tNGS results, and the majority exhibited notable improvement regardless of treatment adjustment. Conclusion: tNGS performs comparably to mNGS and surpasses culture in detecting lower respiratory tract infections. Nevertheless, tNGS is faster and more cost-effective than mNGS, making it highly significant for guiding rational treatment.