
Australian researchers have taken a major step toward using real-time genome sequencing in routine hospital care for patients with severe Staphylococcus aureus infections, or “golden staph,” a superbug responsible for more than 1 million deaths globally each year.
In partnership with seven major Victorian hospitals, researchers from the Peter Doherty Institute for Infection and Immunity (Doherty Institute) have been the first to show that tracking bacterial changes using genome sequencing during serious infection can give clinicians immediate insights to personalize treatment and improve patient outcomes.
Golden staph can cause life-threatening infections such as sepsis, pneumonia, bone and joint infections and endocarditis (infection of the heart valves). The bacteria are known for their ability to adapt quickly, becoming resistant to even the most potent antibiotics. Unlike standard hospital laboratory tests that only identify the type of bacteria, genome sequencing reveals a complete genetic profile, including traits that influence its response to treatment.
Led by The University of Melbourne’s Dr. Stefano Giulieri, Infectious Diseases Physician and Clinician Researcher at the Doherty Institute and lead author of the study published in Nature Communications, the team collected golden staph samples from patients with severe, recurring infections at the time of treatment failure. These strains were compared to strains obtained at the beginning of the infection, with the findings returned to the treating physicians.
Until now, studies on bacterial evolution during infection have only been conducted retrospectively, often years after treatment. While these studies have provided valuable insights to researchers, tracking evolution during infection can be extremely beneficial for clinicians.
Dr. Giulieri said they found that in one-third of the cases, the bacteria had picked up dangerous mutations that made treatment more likely to fail.
“In one case, after initially controlling a golden staph infection, the patient returned to hospital two months after stopping antibiotics,” Dr. Giulieri explained.
“Samples were referred to us for sequencing and we discovered that, during infection, the golden staph bacteria had become 80 times more resistant to the antibiotic used. Each time they reappeared in blood, the bacteria had picked up a new dangerous mutation.
“Using this information, the clinical team was able to choose a new treatment that was able to finally cure the infection.
“Our study is the first to show that by tracking bacterial evolution in real-time, genome sequencing can reveal tricks bacteria use to survive, giving doctors the power to stay one step ahead and tailor treatment to the specific bacterial strain. This helps avoid unnecessary treatments, minimize side effects for patients and prevent further antibiotic resistance—ultimately giving patients the best chance of recovery.”
To assess the value of this approach, the researchers surveyed 25 infectious disease specialists across Australia, Switzerland, the U.K. and the U.S. Clinicians rated the genomic reports as “highly useful” (80 out of 100) and indicated that the information influenced their choice of antibiotic treatment in more than one-third of cases.
Professor Eugene Athan, Infectious Diseases Consultant at University Hospital Geelong and survey participant, said the approach offers the opportunity for infectious diseases to enter the era of precision medicine, just as cancer genomics has done in oncology.
“The ability to track bacterial evolution in real-time during severe infections is a game-changer for clinicians,” said Professor Athan.
The University of Melbourne’s Professor Benjamin Howden, Director of the Microbiological Diagnostic Unit Public Health Laboratory (MDU PHL) at the Doherty Institute and senior author of the study, said this work has significant implications for the future of infectious disease management.
“These findings represent a major step toward targeted therapy for bacterial infections and open the door to future clinical trials that could make this approach standard practice in hospitals worldwide,” said Professor Howden.
As a result of this study, the MDU PHL is exploring a new service to provide advanced genomic investigations for cases where treatment is failing. Victorian hospitals would be the first to access this cutting-edge technology, marking a world-first implementation of precision microbiology in clinical care.
More information:
Stefano G. Giulieri et al, A multi-hospital, clinician-initiated bacterial genomics programme to investigate treatment failure in severe Staphylococcus aureus infections, Nature Communications (2025). DOI: 10.1038/s41467-025-60045-4
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Doctors use real-time genomics to detect golden staph resistance and tailor life-saving therapies (2025, June 4)
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