Metagenomic next‑generation sequencing of BALF for the clinical diagnosis of severe community‑acquired pneumonia in immunocompromised patients: A single‑center study.

Abstract

The diagnostic methods of conventional microbiological tests (CMTs) for severe community-acquired pneumonia (SCAP) may be too complicated or impossible to use in polymicrobial infections, and it may be difficult to identify unexpected pathogens. CMTs are also limited due to the early application of broad-spectrum or prophylactic antimicrobial drugs and the fastidious or slow-growing pathogenic microorganisms. The present study aimed to investigate the value of mNGS compared with CMTs in the clinical diagnosis of SCAP in immunocompromised individuals. Therefore, 37 patients diagnosed with SCAP in immunocompromised adult patients were enrolled from the Respiratory Intensive Care Unit of the First Affiliated Hospital of Soochow University (Soochow, China) between May 1, 2019, and March 30, 2022. A bronchoalveolar lavage fluid sample from each individual was divided in half. Half was sent to the microbiology laboratory directly for examination, and the other one was sent for DNA extraction and sequencing. In addition, other relevant specimens (such as blood) were sent for CMTs, including culture or smear, T-spot, acid-fast stain, antigen detection, multiplex PCR and direct microscopic examination. Based on a composite reference standard, the diagnostic outcomes were compared between CMTs and mNGS. Among the enrolled patients, 31 patients were diagnosed with microbiologically confirmed pneumonia, with 16 (43.2%) having monomicrobial infections, while 15 (40.5%) had polymicrobial infections. Fungi were the most common etiologic pathogens in immunosuppressive individuals. Pneumocystis jirovecii (45.9%) and Aspergillus spp. (18.9%) were the most common etiologic pathogens. Initial screening test validity of mNGS [sensitivity=96.8%; specificity=33.3%; positive predictive value (PPV)=88.2%; negative predictive value (NPV)=66.6%; likelihood ratio (LR)+, 1.45; LR-, 0.10) was higher compared with that of CMTs (sensitivity=38.7%; specificity=82.3; PPV=92.3%; NPV=20.8%; LR+, 2.3; LR-, 0.74). The total diagnostic accuracy of mNGS was superior to CMTs and it was statistically significantly different [86.5% (32/37) vs. 45.9% (17/37); P<0.001]. In conclusion, the total diagnostic accuracy of mNGS was superior to CMTs for SCAP in immunocompromised patients as an important diagnostic method.