Real-time sequencing helps combat golden staph infections

A research team led by The Peter Doherty Institute for Infection and Immunity has taken a major step towards using real-time genome sequencing in routine hospital care, showing that tracking bacterial changes during serious Staphylococcus aureus (golden staph) infection can give clinicians immediate insights to personalise treatment and improve patient outcomes.

Golden staph is a superbug that is responsible for more than one million deaths globally each year. These bacteria can cause life-threatening infections such as sepsis, pneumonia, bone and joint infections, and endocarditis (infection of the heart valves), and 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. But studies on bacterial evolution during infection have until now only been conducted retrospectively, often years after treatment.

The new research in Nature Communications saw scientists from the Doherty Institute, in partnership with seven major Victorian hospitals, collect 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. 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,” said study leader Dr Stefano Giulieri, an infectious diseases physician and clinician researcher at the Doherty Institute.

“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, minimise 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 UK and the US. 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 a third of cases — with survey participant Professor Eugene Athan, an infectious diseases consultant at University Hospital Geelong, saying 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,” Athan said.

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 the 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”. The MDU PHL is now exploring a new service to provide advanced genomic investigations for cases where treatment is failing, which would result in Victorian hospitals becoming the first in the world to access precision microbiology in clinical care.

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