Complementary Utility of Metagenomic Next-Generation Sequencing and Blood Culture for Bloodstream Infections: Insights into Pathogen-Specific Inflammatory and Coagulation Profiles.

BACKGROUND: Bloodstream infections (BSIs) are a major cause of sepsis and mortality in critically ill patients, yet accurate pathogen identification remains challenging because blood culture has limited sensitivity and delayed turnaround time. This study aimed to evaluate the complementary diagnostic value of blood culture and mNGS for BSIs patients, and to identify distinct inflammatory and coagulation signatures across bacterial, viral, fungal and polymicrobial infections to facilitate rapid early pathogen discrimination. METHODS: In this retrospective study, 18,803 patients with suspected BSI admitted between December 2017 and December 2024 were included. Baseline clinical characteristics and blood culture results were collected. Blood culture was performed as first-line testing, whereas mNGS was selectively applied to patients with negative blood cultures or persistent clinically suspected infection to assess its incremental pathogen detection. Differences in pathogen distribution and inflammatory/coagulation biomarkers across pathogen types were analyzed. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of these biomarkers for viral and fungal infections. RESULTS: Compared with blood culture, mNGS provided additional pathogen detection, with newly identified pathogens comprising viruses (33.5%, 184/550), polymicrobial infections (34.9%, 192/550), and fungal pathogens, whereas single bacterial infections accounted for only 14.5% (80/550). Compared with bacterial infections (n=80), viral infections (n=184) were associated with significantly lower procalcitonin (PCT), C-reactive protein (CRP), and fibrinogen (FIB), but higher prognostic nutritional index (PNI) (all p<0.05). Fungal infections (n=57) showed significantly lower PNI and FIB levels (p<0.05) than bacterial infections (n=1098). ROC analysis demonstrated moderate discriminatory performance of PCT, CRP, and FIB for viral infections, while PNI and FIB showed comparable predictive value for fungal infections. CONCLUSION: mNGS complements conventional blood culture by expanding pathogen detection in clinically selected patients, while inflammatory and coagulation biomarkers may assist early etiological assessment and support clinical assessment and antimicrobial decision-making.