Complementary mNGS and traditional testing for bloodstream infections

Bloodstream infections (BSIs) require rapid and accurate etiological diagnosis to guide timely antimicrobial therapy. Conventional diagnostic approaches, particularly blood culture, remain indispensable for antimicrobial susceptibility testing; however, they are limited by prolonged turnaround time and reduced sensitivity, especially following prior antibiotic exposure. Metagenomic next-generation sequencing (mNGS) has emerged as a culture-independent and hypothesis-free diagnostic tool capable of detecting a broad spectrum of pathogens directly from clinical samples. This approach is particularly advantageous for identifying rare, fastidious, and polymicrobial infections, as well as infections in immunocompromised patients. However, its clinical application remains constrained by challenges in distinguishing infection from colonization, interpreting antimicrobial resistance signals, and variability in bioinformatics pipelines. Thus, in the era of integrated diagnosis, mNGS does not replace but powerfully complements traditional methods. Furthermore, we propose a dynamic evidence-weighted integrated diagnostic framework to guide real time clinical decision and improve the clinical applicability of mNGS in bloodstream infections.