Which trial do we need? Next-generation sequencing to individualize therapy in Staphylococcus aureus bacteraemia.

We propose a two-stage clinical trial in patients with Staphylococcus aureus bacteremia (SAB). In Stage 1 we will evaluate metagenomic next generation sequencing from blood as a quantitative biological surrogate for clinical endpoint in patients with SAB, similar to quantitative HIV viral load in HIV-infected patients. In Stage 2, we will conduct a randomized controlled trial to individualize duration of antibiotic therapy for based upon the presence of S. aureus genetic material in patients’ blood. The proposed study addresses two critical aspects of treatment of patients with SAB: the identification of a surrogate biological endpoint for future clinical trials, and a new approach by which to individualize patient management.