Next-generation diagnostics of bloodstream infections enabled by rapid whole-genome sequencing of bacterial cells purified from blood cultures.

Summary

A streamlined real-time LC-WGS workflow identified pathogens directly from positive blood cultures with 98% accuracy in monomicrobial and 88% in polymicrobial samples in about 2.6 hours, and profiled clinically relevant resistance determinants with 94% accuracy in about 4.2 hours. The platform also enabled virulence typing, serotyping, and phylogenomic outbreak analyses.

Key Findings

• Achieved species-level identification in ~2.6 hours with 98% accuracy (65/66) in monomicrobial and 88% (14/16) in polymicrobial blood cultures versus SoC.
• Resistome profiling (allelic variants) was accurate in 94% (58/62) of clinically relevant resistance profiles within ~4.2 hours.
• Enabled in silico serotyping, virulotyping, and comparative phylogenomics for outbreak investigation directly from blood culture material.

Clinical Implications

Clinical labs could integrate LC-WGS to accelerate organism ID and resistance prediction, potentially enabling earlier de-escalation/escalation in sepsis and improving time to appropriate therapy and infection control responses.

Limitations

• Proof-of-concept with a modest sample size from prospectively collected positive blood cultures; clinical outcome impact not assessed.
• Performance in diverse pathogens and direct-from-blood (pre-culture) settings requires further validation.

Future Directions

Multicenter implementation studies linking LC-WGS-guided therapy to time-to-appropriate antibiotics, clinical outcomes, and cost-effectiveness; evaluation in direct-from-blood workflows.