About 30 deaths a year will be prevented in the Hunter, after a clinical trial made a breakthrough in the treatment of golden staph blood infections.
The University of Newcastle co-led the trial, which pinpointed the best antibiotics for these types of infections.
About 350 of these infections occur in the Hunter a year, including about 200 at John Hunter Hospital.
The international study found the standard antibiotic, flucloxacillin, should no longer be the drug of choice to treat the infections.
It found that cefazolin and penicillin were safer and equally effective alternatives for two different golden staph stains.
The antibiotics also had fewer side effects and lower risk of acute kidney injury.
Professor Joshua Davis is an infectious diseases physician at the University of Newcastle and the Hunter Medical Research Institute.
"No one had ever done a trial, so we did one," said Professor Davis, who co-led the global trial.
"In the past, we've been told don't use cefazolin because we don't know for sure if it's going to work. But we found for sure it does work."
Professor Davis said golden staph infections - also known as Staphylococcus aureus septicemia - were "very virulent and common".
"When people get a bloodstream infection or septicemia from that, they have about a 20 per cent chance of dying," he said.
"If that turns into sepsis, the death rate is 40 to 50 per cent."
He said golden staph caused about a million deaths a year globally.
"At John Hunter, we see about 200 patients a year and about 40 deaths," he said.
Professor Davis said golden staph was "the most common cause of every kind of severe bacterial infection".
"That includes septicemia, bone infection, heart infection and skin infections," he said.
"So it's a big deal that we've found the safest and most effective antibiotics for these infections. It will affect millions of patients every year around the world."
Professor Davis said the research will lead to medication guidelines being changed for the treatment of golden staph infections Australia-wide.
"We've been using cefazolin at John Hunter in the last 12 months," he said.
Professor Todd Lee, an infectious diseases physician in Canada who co-led the study, said the next challenge would be changing routine clinical practice globally.
"Cefazolin availability may need to increase in some countries," Professor Lee said.
He said changing treatment would "ultimately depend on hospitals, laboratories and guideline groups incorporating the findings into clinical care".
The trial was the world's largest study of golden staph infections.
It involved about 1800 patients from Australia, Canada, France, Germany, Israel, Japan, Malaysia, the Netherlands, New Zealand, Singapore, South Africa, Sweden, the UK and US.
Professor Steven Tong, an infectious diseases physician at the Doherty Institute, said there were fewer deaths within 90 days.
Professor Tong, who co-led the study, said 15 per cent of patients treated with cefazolin died, compared to 17 per cent of those who received flucloxacillin.
In the study, 14 per cent of patients treated with cefazolin suffered an acute kidney injury, compared to 21 per cent with flucloxacillin.
Affected patients can end up needing dialysis.
Professor Davis said the change in antibiotics would prevent 20 to 30 cases of acute kidney injury a year at John Hunter, and 35 to 50 across the region.
The trial involved two studies, one published in the New England Journal of Medicine and the other in The Lancet.
The first study compared cefazolin and flucloxacillin for the most common strain of golden staph.
The second study, which examined the original strain of golden staph, compared penicillin and flucloxacillin.
"Patients treated with penicillin experienced less kidney damage, with mortality also lower at 14 per cent compared with 22 per cent in the flucloxacillin group," Professor Lee said.
