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

Metagenomic sequencing could potentially revolutionise clinical microbiology, including identifying pathogens and predicting antimicrobial resistance (AMR) in seriously unwell patients with bloodstream infections. We present a direct-from-blood culture sequencing method that delivers results rapidly and accurately. In 273 randomly-selected blood cultures (211 positive, 62 negative), we achieved 97% sensitivity and 94% specificity (improving to 100% accounting for plausible additional infections) for species identification compared to established diagnostic methods. We detected 18 additional infections—13 polymicrobial and 5 previously unidentifiable—and delivered findings in 3.5 hours, nearly a third of time taken by routine methods. For the top ten pathogens, our method produced AMR results 20 hours quicker, with 88% sensitivity and 93% specificity. For Staphylococcus aureus and Escherichia coli , AMR prediction sensitivity was 100% and 91%, and specificity 99% and 94% respectively. These findings suggest the potential of integrating clinical metagenomics into standard diagnostics for faster and more comprehensive pathogen detection.