A multi-hospital, clinician-initiated bacterial genomics program to investigate treatment failure in severe Staphylococcus aureus infections

Bacterial genomics is increasingly used for infectious diseases surveillance, outbreak control 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 novel clinician-driven bacterial genomics framework that applies within-patient evolutionary analysis to identify in real-time microbial genetic changes that have an impact on the outcome of severe Staphylococcus aureus infections, a strategy that is increasingly used in cancer genomics. Our approach uses a combination of bacterial genomics and novel microbiological testing to identify and track bacterial adaptive mutations that underlie antibiotic treatment failure. We show real-life examples of the impact of our approach and propose a roadmap for the use of bacterial genomics to advance the management of severe bacterial infections. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by a National Health and Medical Research Council (NHMRC) grant (APP1196103) to B.P.H. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: University of Melbourne Human Research Ethics Committee gave approval for this work (reference number 1954615.3) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors