Sequence-based approaches for rapid diagnosis of bacterial sepsis

Sepsis is a common medical emergency in acute hospital settings worldwide. It is a life threatening organ dysfunction that can be triggered by a range of pathogens. The UK Sepsis Trust estimates there are around 250,000 cases of sepsis in the UK each year, and at least 46,000 deaths. Early case recognition and rapid administration of antibiotics can reduce mortality by preventing progression. However, identification of the specific bacteria causing sepsis currently requires at least 2-day culture. Until then, physicians rely on broad-spectrum antibiotics. A reliable and rapid diagnostic test would facilitate faster identification of the bacteria causing infection, allowing targeted antibiotic therapy to be initiated within a clinically relevant timeframe.

We are developing a protocol that uses MinION sequencing to determine the bacterial causes of sepsis from blood samples with the aim of rapidly informing targeted antimicrobial treatment. This involves selectively depleting host DNA and then amplifying residual bacterial DNA to improve sensitivity of sequence-based diagnostics in bloodstream infections, which typically have a low bacterial load. This project represents an important step towards improving patient outcomes and helping prevent the development of antimicrobial resistance by facilitating judicious use of antibiotics.