A multi-hospital, clinician-initiated bacterial genomics programme to investigate treatment failure in severe Staphylococcus aureus infections
- Stefano G. Giulieri
- Marcel Leroi
- Diane Daniel
- Roy Chean
- Katherine Bond
- Harry Walker
- Natasha E. Holmes
- Nomvuyo Mothobi
- Adrian Alexander
- Adam Jenney
- Carolyn Beckett
- Andrew Mahony
- Kerrie Stevens
- Norelle L. Sherry
- Benjamin P. Howden
2025-05-26
Bacterial genomics is increasingly used for infectious diseases surveillance, outbreak detection and prediction of antibiotic resistance. With expanding availability of rapid whole-genome sequencing, bacterial genomics data could become a valuable tool for clinicians managing bacterial infections, driving precision medicine strategies. Here, we present a clinician-driven bacterial genomics framework that applies within-patient evolutionary analysis to identify in real-time microbial genetic changes that have an impact on treatment outcomes of severe Staphylococcus aureus infections, a strategy that is increasingly used in cancer genomics. Our approach uses a combination of bacterial genomics and antibiotic susceptibility testing to identify and track bacterial adaptive mutations that underlie microbiologically documented treatment failure (i.e. ongoing positive cultures [persistent infection] or new positive cultures after initial response [recurrent infection]). We show the potential added value of our approach to clinicians and propose a roadmap for the use of bacterial genomics to advance the management of severe bacterial infections.