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 nextgeneration 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.