newy.com.au – University of Newcastle researchers have helped identify safer first-line antibiotics for life-threatening golden staph bloodstream infections, with a major international trial finding flucloxacillin should no longer be the default treatment.
The Staphylococcus aureus Network Adaptive Platform Trial, known as SNAP, found cefazolin was at least as effective as flucloxacillin for methicillin-susceptible Staphylococcus aureus infections and caused fewer cases of acute kidney injury. Benzylpenicillin was also favoured for infections confirmed by laboratory testing to be susceptible to penicillin.
The antibiotic comparisons involved more than 1600 patients at more than 90 hospitals in eight countries. The broader SNAP Trial, co-led by the University of Newcastle and Melbourne’s Peter Doherty Institute for Infection and Immunity, operates across more than 150 hospitals in more than 14 countries.
Golden staph can cause serious illness when it enters the bloodstream, with researchers estimating that between 15 and 25 per cent of patients with bloodstream infections die. Golden staph infections are linked to more than one million deaths worldwide each year, but uncertainty has persisted over which available antibiotic produces the best outcomes.
In the cefazolin comparison, 15 per cent of patients died within 90 days, compared with 17 per cent of those treated with flucloxacillin or cloxacillin. Acute kidney injury occurred in about 14 per cent of cefazolin patients and almost 20 per cent of those given the other drugs. The findings, published in the New England Journal of Medicine, showed cefazolin was no less effective and carried a lower risk of kidney injury.
SNAP global co-lead investigator Professor Steven Tong said there was an 89 per cent probability cefazolin was associated with lower mortality in patients with methicillin-susceptible infections.
“The results are sufficiently compelling that I immediately made the switch in my own clinical practice,” Professor Tong said.
A second study, published in The Lancet, examined benzylpenicillin in patients whose infections were confirmed as penicillin-susceptible. Mortality was 14 per cent among patients treated with benzylpenicillin, compared with 22 per cent in the flucloxacillin or cloxacillin group, while kidney damage was also less common.
Although the benzylpenicillin comparison did not reach its pre-set statistical threshold for non-inferiority, recruitment was halted after safety monitors detected increased acute kidney injury among patients receiving flucloxacillin or cloxacillin. The researchers concluded the probability of comparable mortality, together with the lower kidney risk, supported using benzylpenicillin for susceptible infections.
University of Newcastle infectious diseases physician and SNAP global co-lead investigator Professor Joshua Davis said the results supported carefully reintroducing penicillin for strains that remained susceptible.
“These findings show clinicians can confidently use penicillin susceptibility results to guide treatment where laboratory testing is available,” Professor Davis said.
Researchers said hospitals, laboratories and clinical guideline groups would now need to incorporate the evidence into routine care, while access to cefazolin may need to increase in some countries.
