Diagnostic Performance and Clinical Impact of Metagenomic Next-Generation Sequencing in 841 Patients with Suspected Lower Respiratory Tract Infections: A Four-Year Retrospective Study from a Tertiary Hospital in Shenzhen, China

BACKGROUND: Accurate pathogen identification is critical for managing lower respiratory tract infections (LRTIs), particularly in suspected polymicrobial infection or after empiric treatment failure. Although metagenomic next-generation sequencing (mNGS) has been increasingly used in clinical practice, its long-term diagnostic performance and clinical impact in LRTIs have not been systematically evaluated in a large single-center cohort. METHODS: We conducted a retrospective cohort study of 841 hospitalized patients with suspected LRTIs who underwent bronchoalveolar lavage fluid (BALF) testing by both mNGS and conventional culture between December 2021 and December 2025. Positive detection rates, polymicrobial identification, pathogen distributions across age and underlying disease categories, method concordance, and clinical impact were evaluated. RESULTS: mNGS yielded significantly higher overall and polymicrobial detection rates than culture. Pathogen profiles differed between mNGS and culture and varied across age and underlying diseases subgroups. Over half of pathogens were identified exclusively by mNGS, and over half of these mNGS-exclusive detections influenced diagnostic and antimicrobial management. Furthermore, Mycobacterium tuberculosis complex, nontuberculous mycobacteria, Cryptococcus neoformans, and Pneumocystis jirovecii retained clinical significance even at low sequencing read counts. CONCLUSIONS: In this real-world cohort, mNGS expanded pathogen detection, improved recognition of mixed infections, and provided meaningful clinical value in LRTI.