More than one million deaths per year are caused by golden staph infections, the most serious form being when it enters the bloodstream — with a mortality rate of 15 to 25%. There are effective antibiotics to treat the bloodstream infections; however, uncertainty has remained over which treatments lead to the best patient outcomes.

To address this, 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 — set out to evaluate different antibiotics and treatment strategies to reduce mortality and improve patient outcomes.

In the trial’s findings, published in the New England Journal of Medicine (NEJM) and The Lancet, the long-held assumption that flucloxacillin should remain the default treatment is challenged, and, the researchers say, new evidence to guide treatment strategy is provided.

MSSA infections

In the NEJM study (doi.org/10.1056/NEJMoa2506905), which compared antibiotics used to treat methicillin-susceptible Staphylococcus aureus (MSSA) infections, cefazolin was found to be at least as effective as flucloxacillin and associated with fewer side effects and a lower risk of kidney injury.

“In the treatment of MSSA bloodstream infections, there is an 89% probability that cefazolin is associated with lower mortality,” said The Royal Melbourne Hospital’s Professor Steven Tong, an Infectious Diseases Physician at the Doherty Institute.

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

PSSA infections

In The Lancet study (doi.org/10.1016/S0140-6736(26)00761-0), it was evaluated whether benzylpenicillin could be used to treat penicillin-susceptible Staphylococcus aureus (PSSA) infections where laboratory testing confirmed the susceptibility to penicillin. What was found was that benzylpenicillin was as effective as flucloxacillin and likely safer.

This is according to Professor Todd Lee, a scientist at the Research Institute of the McGill University Health Centre and Infectious Diseases and Internal Medicine Physician at the McGill University Health Centre in Canada who was co-lead investigator of both studies.

“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 in clinical practice

Penicillin was once widely used to treat Staphylococcus aureus, but antibiotic resistance of golden staph led clinicians to adopt flucloxacillin as the standard treatment for MSSA and PSSA infections. The above results, the researchers said, mark a turning point in the treatment of MSSA and PSSA bloodstream infections, signalling a shift in clinical practice — supporting a move away from flucloxacillin as the default treatment, given safer and equally effective alternatives are available.

“These findings show clinicians can confidently use penicillin susceptibility results to guide treatment where laboratory testing is available,” said Professor Joshua Davis, an Infectious Diseases Physician at the University of Newcastle and Australia’s Hunter Medical Research Institute in Australia, and global co-lead investigator of the SNAP Trial.

Translating the findings into routine clinical practice will be the next challenge, the researchers said, adding that, while cefazolin availability may need to increase in some countries, 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 said. “Trials generate the evidence, but the next step is making sure that evidence changes practice.”

You can learn more about the trial at www.snaptrial.com.au.

Image credit: iStock.com/Alexander Maniakhin

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