High utility of BALF Metagenomic Next-Generation Sequencing Approach for Etiological Diagnosis of Pneumonia

Background : For patients with pneumonia, rapid detection of pathogens is still a major global problem in clinical practice because traditional diagnostic techniques for infection are time-consuming and insensitive. Metagenomic next-generation sequencing (mNGS) is a novel technique that has the potential to improve pathogen diagnosis. In this study, we aimed to explore the microbiological diagnostic ability of mNGS compared with that of conventional culture in pneumonia patients and to explore the best opportunityto test. Methods: A prospective study from June 2020 to June 2021 was performed at a tertiary teaching hospital in China, and 56 pneumonia patients were included among all adult patients with a clinical diagnosis of pneumonia. Blood and bronchoalveolar lavage fluid (BALF) samples were taken for simultaneous mNGS and conventional culture testing. Results: All 56 patients underwent both conventional culture and mNGS, 37 of whom were diagnosed with severe pneumonia and 17 of whom were diagnosed with nonsevere pneumonia. The top three pathogenic bacteria detected by mNGS were Acinetobacter baumannii , Klebsiella pneumoniae and Pseudomonas aeruginosa . Enterococcus faecium was detected more frequently in the non-severepneumonia group (4 vs. 0, p<0.05). The findings revealed that the detection rate of mNGS (84%) was superior to that of conventional culture methods (48%). Notably, the percentage of mNGS-positive BALF samples (46/56, 82.14%) was significantly greater than that ofblood samples (27/56, 48.21%). The etiological comparison demonstrated that mNGS-positive samples for which clinical approval was obtained tended to be associated with a more normalized temperature, lower PCO2 levels, and a higher SOFA score thanmNGS-negative samples (p= 0.022, p = 0.0.028, and p = 0.038, respectively). Conclusions: In this study, we discovered that the etiology of lung infections frequently involves multiple pathogens. mNGS of BALF is instrumental for detecting nonviral pathogens associated with lung infections. Although the rate of positive blood NGS results is significantly influenced by various clinical factors, for patients suspected of having viral, Legionella, or tsutsugamushi infections, plasma mNGS could serve as a complementary diagnostic tool.