Optimising Treatment Outcomes for Children and Adults Through Rapid Genome Sequencing of Sepsis Pathogens. A Study Protocol for a Prospective, Multi-Centre Trial (DIRECT)

Irwin, A. D., et al. (2021). "Optimising Treatment Outcomes for Children and Adults Through Rapid Genome Sequencing of Sepsis Pathogens. A Study Protocol for a Prospective, Multi-Centre Trial (DIRECT)." Frontiers in Cellular and Infection Microbiology

Background: Sepsis contributes significantly to morbidity and mortality globally. In Australia, 20,000 develop sepsis every year, resulting in 5,000 deaths, and more than AUD$846 million in expenditure. Prompt, appropriate antibiotic therapy is effective in improving outcomes in sepsis. Conventional culture-based methods to identify appropriate therapy have limited yield and take days to complete. Recently, nanopore technology has enabled rapid sequencing with real-time analysis of pathogen DNA. We set out to demonstrate the feasibility and diagnostic accuracy of pathogen sequencing direct from clinical samples, and estimate the impact of this approach on time to effective therapy when integrated with personalised software-guided antimicrobial dosing in children and adults on ICU with sepsis.

Methods: The DIRECT study is a pilot prospective, non-randomized multicentre trial of an integrated diagnostic and therapeutic algorithm combining rapid direct pathogen sequencing and software-guided, personalised antibiotic dosing in children and adults with sepsis on ICU.