Hongfei Zheng,1,* Pei Peng,2,3,* Shaofei Wang,1 Bo Zhang,1 Linying Yang,1 Yaoyao Wang,2,3 Lejun Li,4 Guifen Pang1 

1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical College, Chengde, 67000, People’s Republic of China; 2Shanghai Biotecan Pharmaceuticals Co., Ltd, Shanghai, 201204, People’s Republic of China; 3Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, 201204, People’s Republic of China; 4Department of Neurology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215008, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lejun Li, Department of Neurology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215008, People’s Republic of China, Email lilejjun999@163.com Guifen Pang Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengde Medical College, Chengde, 67000, People’s Republic of China, Tel +86 15633142975, Email 15633142975@163.com

Objective: Community-acquired pneumonia (CAP) presents a significant public health concern, necessitating timely and precise diagnosis. Metagenomic next-generation sequencing (mNGS) has shown promise as a powerful tool for pathogen identification in infectious diseases. This study aimed to evaluate the diagnostic efficacy and clinical applicability of mNGS for immunocompromised patients with CAP compared to the culture method.
Methods: This study included 168 patients. We used both mNGS and conventional culture methods to identify the pathogen spectrum and evaluate diagnostic performance. Treatment regimens and clinical outcomes were meticulously documented.
Results: The sensitivity of mNGS was greater than that of the culture method across all samples (79.05% vs 16.03%; p < 0.001). mNGS identified pathogens missed by culture in 59.52% of patients and detected polymicrobial infections that were not detected by culture in 47.62% of patients. Streptococcus pneumoniae, Candida albicans, and Human herpesvirus 4 at classification level emerged as the predominant pathogens identified in CAP patients through mNGS. When examining the mNGS results between groups, the proportions of immunocompromised patients with bacterial (p < 0.001), fungal (p < 0.001), viral (p < 0.05), and mixed infections (p < 0.001) were all significantly higher than those in immunocompetent patients. Treatment adjustments guided by mNGS were observed in 73.21% of patients. Specifically, a beneficial clinical effect was observed in 50.60% (85/168) of patients, treatment confirmation in 22.62% (38/168) of patients, and no clinical benefit in 26.80% (45/168) of patients based on mNGS-guided antibiotic treatment adjustments.
Conclusion: These findings highlight the diagnostic performance of mNGS for identifying pathogens, particularly in immunocompromised patients vulnerable to infections, offering valuable insights for clinical decision-making.

Keywords: diagnostic performance, clinical effect, immunocompromised, community-acquired pneumonia, metagenomic next-generation sequencing