Evaluation of Cell-Free DNA-Based Next-Generation Sequencing for Identifying Pathogens in Bacteremia Patients

Rapid detection of bloodstream pathogens would greatly facilitate clinicians to make precise antimicrobial treatment in patients with bacteremia. In this study, 114 plasma samples were collected from patients with identified or suspected bacteremia, and pathogens were detected by the conventional blood culture (BC) and cell-free DNA metagenomics next-generation sequencing (cfDNA mNGS). The present study indicated that 76% (38/50) of positive conventional blood culture (BC+ group) patients were positively detected by cfDNA mNGS, and only 4% were mismatched between cfDNA mNGS and conventional bacteria culture. Pathogens in 32.8% of suspected bacteremia patients with negative conventional blood culture (BC- group) were determined accurately by cfDNA mNGS combined with analyzing the patients' clinical manifestations. Escherichia coli and Klebsiella pneumoniae were the most detected pathogens in identified bacteremia patients by cfDNA mNGS. 76.2% (16/21) of E. coli and 92.3% (12/13) of K. pneumoniae in bacteremia patients were identified by conventional blood cultures that were also detected by cfDNA mNGS. This study demonstrated that genomic coverage of E. coli and K. pneumoniae were more often detected in BC+ group patients and genomic coverage of Acinetobacter johnsonii and Paucibacter sp. KCTC 42545 was more often detected in BC- group patients. In conclusion, cfDNA mNGS could rapidly and precisely provide an alternative detection method for the diagnosis of bacteremia.