Global Trial Finds Safer Antibiotic Alternatives for Golden Staph Bloodstream Infections

"Cefazolin should be considered the first-line option for MSSA bloodstream infections."

Major Clinical Trial Identifies Safer, Equally Effective Alternatives to Standard Staph Treatment

A large international clinical trial has identified two alternative antibiotics, cefazolin and benzylpenicillin, as safer and equally effective treatments for bloodstream infections caused by Staphylococcus aureus (golden staph) compared to the standard therapy, flucloxacillin. The findings were published in The New England Journal of Medicine and The Lancet.

Trial Overview

The Staphylococcus aureus Network Adaptive Platform Trial (SNAP Trial) is the largest international study ever conducted on S. aureus bloodstream infections. Co-led by the Peter Doherty Institute for Infection and Immunity, the University of Newcastle (Australia), and the Research Institute of the McGill University Health Centre (Canada), the trial monitored patients across more than 150 hospitals in 14 countries, including Australia, Canada, the United States, and the United Kingdom.

Key Findings

The study compared cefazolin and flucloxacillin for treating methicillin-susceptible Staphylococcus aureus (MSSA) infections.

Mortality: 15% of patients treated with cefazolin died within 90 days, compared to 17% for those treated with flucloxacillin.
Kidney Injury: 14% of patients receiving cefazolin developed acute kidney injury, compared to 20% for those receiving flucloxacillin.
Analysis: The data indicated an 89% probability that cefazolin is associated with lower mortality.

The study evaluated benzylpenicillin for penicillin-susceptible Staphylococcus aureus (PSSA) infections.

• Mortality: 14% of patients treated with benzylpenicillin died within 90 days, compared to 22% for those treated with flucloxacillin.
• Kidney Injury: Less kidney damage was observed in the benzylpenicillin group compared to the flucloxacillin group.

Background

Staphylococcus aureus bloodstream infections cause over one million deaths globally each year, with a reported mortality rate of 15-25%. In Australia, approximately 4,000 patients annually contract the serious bloodstream form of the infection. While about one-third of people carry the bacteria harmlessly in their noses, serious infections can occur when it enters the bloodstream. Historically, penicillin was used to treat S. aureus, but the development of antibiotic resistance led to flucloxacillin becoming the standard treatment.

Expert Statements

Professor Steven Tong, an infectious diseases physician at the Doherty Institute and co-lead investigator, stated that cefazolin should be considered the first-line option for MSSA bloodstream infections and reported that he has switched his own clinical practice. He noted that the lower mortality rate associated with cefazolin was surprising.

Professor Todd Lee from McGill University, a co-lead investigator, stated: "The findings challenge the long-held assumption that cloxacillin is the best treatment. Benzylpenicillin is as effective and likely safer."

Professor Joshua Davis from the University of Newcastle stated that clinicians can confidently use penicillin susceptibility results to guide treatment decisions where laboratory testing is available.

Infectious diseases expert Robert Booy, who was not involved in the research, stated that the trial will help shape treatment options and enhance outcomes.

Implementation and Next Steps

Researchers noted that translating these findings into widespread clinical practice will require adjustments in hospital prescribing practices, updates to clinical guidelines, and increased availability of cefazolin in some countries. The research has already led to a change in clinical practice at the Royal Melbourne Hospital, which treats approximately two cases of serious golden staph bloodstream infections per week.