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 and Benjamin P. Howden
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Stefano G. Giulieri: The University of Melbourne at the Doherty Institute for Infection and Immunity
Marcel Leroi: Austin Health
Diane Daniel: The University of Melbourne at the Doherty Institute for Infection and Immunity
Roy Chean: Eastern Health
Katherine Bond: The University of Melbourne at the Doherty Institute for Infection and Immunity
Harry Walker: Dorevitch Pathology
Natasha E. Holmes: Austin Health
Nomvuyo Mothobi: University Hospital Geelong
Adrian Alexander: The Alfred Hospital
Adam Jenney: The Alfred Hospital
Carolyn Beckett: Epworth HealthCare
Andrew Mahony: Austin Health
Kerrie Stevens: The University of Melbourne at the Doherty Institute for Infection and Immunity
Norelle L. Sherry: The University of Melbourne at the Doherty Institute for Infection and Immunity
Benjamin P. Howden: The University of Melbourne at the Doherty Institute for Infection and Immunity

Nature Communications, 2025, vol. 16, issue 1, 1-9

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-60045-4

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