Abstract Background Metagenomic next-generation sequencing (mNGS) provides innovative solutions for predicting complex infections. A comprehensive understanding of its strengths and limitations in real-world clinical settings is necessary to ensure that it is not overused or misinterpreted. Methods Two hundred nine cases with suspected pneumonia were recruited to compare the capabilities of 2 available mNGS assays (bronchoalveolar lavage fluid [BALF] mNGS and plasma mNGS) to identify pneumonia-associated DNA/RNA pathogens and predict antibiotic resistance. Results Compared to clinical diagnosis, BALF mNGS demonstrated a high positive percent agreement (95.3%) but a low negative percent agreement (63.1%). Plasma mNGS revealed a low proportion of true negatives (30%) in predicting pulmonary infection. BALF mNGS independently diagnosed 65.6% (61/93) of coinfections and had a remarkable advantage in detecting caustic, rare, or atypical pathogens. Pathogens susceptible to invasive infection or bloodstream transmission, such as Aspergillus spp, Rhizopus spp, Chlamydia psittaci , and human herpesviruses, are prone to be detected by plasma mNGS. BALF mNGS tests provided a positive impact on the diagnosis and treatment of 128 (61.2%) patients. Plasma mNGS, on the other hand, turned out to be more suitable for diagnosing patients who received mechanical ventilation, developed severe pneumonia, or developed sepsis (all P < .01). BALF mNGS was able to identify resistance genes that matched the phenotypic resistance of 69.4% (25/36) of multidrug-resistant pathogens. Conclusions Our data reveal new insights into the advantages and disadvantages of 2 different sequencing modalities in pathogen identification and antibiotic resistance prediction for patients with suspected pneumonia.
【저자키워드】 Pneumonia, Metagenomic next-generation sequencing, mNGS, antibiotic resistance gene,