Rapid clinical diagnosis and treatment of common, undetected, and uncultivable bloodstream infections using metagenomic sequencing from routine blood cultures with Oxford Nanopore

Metagenomic sequencing is poised to revolutionise clinical microbiology, especially for identifying pathogens and predicting antimicrobial resistance (AMR) in bloodstream infections. Our study presents a direct-from-blood culture sequencing method that delivers results rapidly and accurately. In randomised testing of 273 blood samples (211 positive, 62 negative), we achieved 97% sensitivity and 94% specificity, which improved to 100% upon re-evaluation of plausible infections. Importantly, we detected 18 additional infections—including 13 polymicrobial and 5 previously unidentifiable—and delivered findings in just 3 hours and 30 minutes, nearly a third of time taken by routine methods. For the top ten pathogens, our method offered AMR results 20 hours quicker, with 88% sensitivity and 93% specificity. Specifically, for Staphylococcus aureus and Escherichia coli, sensitivity was 100% and 91%, with specificities of 99% and 94% respectively. These findings suggest the potential of integrating clinical metagenomics into standard diagnostics for faster and more comprehensive pathogen detection.