Global clinical trial reveals safest, most effective antibiotics for golden staph bloodstream infections

An international clinical trial has identified the optimal antibiotics for golden staph bloodstream infections, a breakthrough set to reshape treatment for the life-threatening condition. The SNAP Trial found that the standard antibiotic, flucloxacillin, should no longer be the drug of choice for treating the infection, revealing that cefazolin and benzylpenicillin offer safer and equally effective alternatives for patients.

The Staphylococcus aureus Network Adaptive Platform Trial (SNAP Trial), led by researchers at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and the University of Newcastle, is the largest international clinical trial ever conducted for golden staph (Staphylococcus aureus) infections, involving more than 150 hospitals in more than 14 countries. The multicenter trial rapidly evaluates different antibiotics and treatment strategies to reduce mortality and improve patient outcomes.

Golden staph infections cause more than 1 million deaths a year. The most serious form of golden staph infection occurs when it enters the bloodstream, with a mortality rate of 15% to 25%. While effective antibiotics are available to treat bloodstream infections, uncertainty has remained over which treatments lead to the best patient outcomes.

Findings from the SNAP Trial, published in the New England Journal of Medicine (NEJM) and The Lancet, challenge the long-held assumption that flucloxacillin should remain the default treatment and provide important new evidence to guide treatment strategies.

The NEJM study—Comparing cefazolin and flucloxacillin

In the study published in the New England Journal of Medicine, researchers compared antibiotics used to treat methicillin-susceptible Staphylococcus aureus (MSSA) infections. They found that cefazolin is at least as effective as flucloxacillin but is associated with fewer side effects and a lower risk of kidney injury.

The Royal Melbourne Hospital’s Professor Steven Tong, an infectious diseases physician at the Doherty Institute in Australia and global co-lead investigator of the SNAP Trial, said the results provide clear evidence that cefazolin should be considered the first-line option for treating MSSA bloodstream infections.

“In the treatment of MSSA bloodstream infections, there is an 89% probability that cefazolin is associated with lower mortality,” Tong said. “Patients treated with cefazolin fare better, with fewer deaths within 90 days (15% compared to 17% for those who received flucloxacillin). Cefazolin was also associated with fewer cases of acute kidney injury, at 14%, compared to 20% with flucloxacillin.

“The results are sufficiently compelling that I immediately made the switch in my own clinical practice.”

The Lancet study—Comparing benzylpenicillin and flucloxacillin

In the paper published in The Lancet, the study evaluated whether benzylpenicillin could be used to treat penicillin-susceptible Staphylococcus aureus (PSSA) infections when laboratory testing confirmed susceptibility to penicillin.

Professor Todd Lee, a scientist at the Research Institute of the McGill University Health Center and an infectious diseases and internal medicine physician at the McGill University Health Center in Canada and co-lead investigator of both studies, said benzylpenicillin was as effective as flucloxacillin and likely safer.

“Patients treated with benzylpenicillin experienced less kidney damage, with mortality also lower at 14% compared with 22% in the flucloxacillin group,” Lee said.

A shift away from flucloxacillin

Researchers said these results mark a turning point in the treatment of MSSA and PSSA bloodstream infections, signaling a shift in clinical practice.

Penicillin was once widely used to treat Staphylococcus aureus, but golden staph’s antibiotic resistance led clinicians to adopt flucloxacillin as the standard treatment for MSSA and PSSA infections.

The findings support moving away from flucloxacillin as the default treatment for MSSA and PSSA infections, given that safer and equally effective alternatives are available.

Professor Joshua Davis, an infectious diseases physician at the University of Newcastle and the Hunter Medical Research Institute in Australia, and global co-lead investigator of the SNAP Trial, said some strains are once again susceptible to penicillin, renewing interest in carefully reintroducing older antibiotics.

“These findings show clinicians can confidently use penicillin susceptibility results to guide treatment where laboratory testing is available,” Davis said.

Lyn Whiteway, a sepsis survivor and consumer representative on both trials, welcomed the findings. “The SNAP Trial shows what is possible when patients are truly at the center of research. These findings will save lives and spare people from unnecessary harm,” Whiteway said.

Translating the findings

Researchers say the next challenge will be translating the findings into routine clinical practice.

While cefazolin availability may need to increase in some countries, researchers say implementation will ultimately depend on hospitals, laboratories and guideline groups incorporating the findings into clinical care.

“This is the largest trial ever conducted on staphylococcal bloodstream infections. It brought together countries from all over the world to answer important questions and improve care for millions of people,” Lee added.

“Trials generate the evidence, but the next step is making sure that evidence changes practice.”

Who’s behind this story?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021.

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Robert Egan

Bachelor’s in mathematical biology, Master’s in creative writing. Well-traveled with unique perspectives on science and language.

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