June 18, 2026
South African researchers at the Clinical Health Research Unit (CHRU) at the University of the Witwatersrand have contributed to a landmark global trial that has identified the safest and most effective antibiotics for life-threatening golden staph bloodstream infections. CHRU was the only low- and middle-income country site in the study, recruiting patients from Helen Joseph Hospital in Johannesburg. The findings, now published in both The New England Journal of Medicine and The Lancet, are expected to influence treatment decisions in South Africa as well as internationally.
The SNAP Trial showed that flucloxacillin should no longer be the default treatment for these infections, with cefazolin and benzylpenicillin emerging as safer, equally effective alternatives depending on the type of infection.
Clinical Health Research Unit (CHRU) / Doherty Institute / University of Newcastle
Media release
Global clinical trial reveals safest, most effective antibiotics for golden staph bloodstream infections
Thursday, 18 June 2026: A landmark international clinical trial has identified the optimal antibiotics for golden staph bloodstream infections, a breakthrough that is 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 to treat the infection, revealing that cefazolin and benzylpenicillin offer safer and equally effective alternatives to 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 across more than 14 countries. The multi-centre trial rapidly evaluates different antibiotics and treatment strategies to reduce mortality and improve patient outcomes.
The Clinical Health Research Unit (CHRU) at the University of the Witwatersrand was the only low- and middle-income country (LMIC) site participating in this research, recruiting patients from Helen Joseph Hospital in Johannesburg.
Golden staph infections cause over one million deaths per year. The most serious form of golden staph infections is when it enters the bloodstream, with a mortality rate of 15 to 25 per cent. The burden is disproportionately higher in low- and middle-income countries like South Africa. While there are effective antibiotics to treat bloodstream infections, uncertainty has remained over which treatments lead to the best patient outcomes.
Findings from the SNAP Trial, published today 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 strategy.
The NEJM study – Comparing cefazolin and flucloxacillin
In the study published in the NEJM, researchers compared antibiotics used to treat methicillin-susceptible Staphylococcus aureus (MSSA) infections. They found that cefazolin is at least as effective as flucloxacillin, but associated with fewer side effects and a lower risk of kidney injury.
Dr Tom Boyles, senior researcher at CHRU, said the inclusion of a South African site was crucial for ensuring the findings apply to patients across different healthcare settings globally.
"Our participation in SNAP demonstrates that high-quality clinical trial research can be conducted in resource-constrained settings," said Dr Boyles. "Between August 2023 and May 2025, we successfully enrolled 28 participants with 100% follow-up completion, proving that LMIC sites can contribute valuable data to global research efforts."
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 to treat MSSA bloodstream infections.
“In the treatment of MSSA bloodstream infections, there is an 89 per cent probability that cefazolin is associated with lower mortality,” said Professor Tong.
“Patients treated with cefazolin fare better, with fewer deaths within 90 days (15 per cent compared to 17 per cent for those who received flucloxacillin). Cefazolin was also associated with fewer cases of acute kidney injury, at 14 per cent, compared to 20 per cent with flucloxacillin.
“The results are sufficiently compelling that I immediately made the switch in my own clinical practice.”
Dr Boyles emphasised the importance of including diverse populations in clinical research: "The high disease burden we see in our setting, combined with our cost-effective operations, reinforces why LMIC participation is both strategically important and ethically imperative. These findings will directly benefit South African patients and healthcare systems."
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 where laboratory testing confirmed the susceptibility to penicillin.
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 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 per cent compared with 22 per cent in the flucloxacillin group,” said Professor Lee.
A shift away from flucloxacillin
Researchers said these results mark a turning point in the treatment of MSSA and PSSA bloodstream infections, signalling 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 findings support moving away from flucloxacillin as the default treatment for MSSA and PSSA infections, given 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,” said Professor Davis.
Dr Boyles emphasised the importance of including diverse populations in clinical research: "The high disease burden we see in our setting, combined with our cost-effective operations, reinforces why LMIC participation is both strategically important and ethically imperative. These findings will directly benefit South African patients and healthcare systems."
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 centre of research. These findings will save lives and spare people from unnecessary harm,” said Ms Whiteway.
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,” added Professor Lee.
“Trials generate the evidence, but the next step is making sure that evidence changes practice.”
ENDS
NOTES TO EDITORS
- The SNAP Trial is a major Australia-led global clinical study investigating the most effective treatments for Staphylococcus aureus bloodstream infections across all age groups.
- This trial is the world’s largest study ever undertaken to improve treatment for Staphylococcus aureus infections.
- So far in the over-arching SNAP Trial, participants have been enrolled in Australia, Canada, France, Germany, Israel, Japan, Malaysia, the Netherlands, New Zealand, Singapore, South Africa, Sweden, the United Kingdom and the United States. The trial will continue testing new approaches to improve outcomes for patients facing this serious infection.
- Professor Tong (Doherty Institute, Australia), Professor Josh Davies (The University of Newcastle, Australia), Professor Todd Lee (McGill University Health Centre and Infectious Diseases, Canada), as well as consumer representatives for these studies are available for interviews. See contact details below.
Peer-reviewed papers:
- The Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Group. Cefazolin for Methicillin-Susceptible Staphylococcus aureus bacteremia. The New England Journal of Medicine (NEJM) (2026). DOI: http://doi.org/10.1056/NEJMoa2506905
- The Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Group. Benzylpenicillin versus flucloxacillin or cloxacillin for the treatment of penicillin-susceptible Staphylococcus aureus bacteraemia (SNAP): an international, multicentre, open-label, non-inferiority randomised controlled trial. The Lancet (2026). DOI: https://doi.org/S0140-6736(26)00761-0
Funding: This study was supported by the National Health and Medical Research Council (NHMRC) and Medical Research Future Fund (MRFF) in Australia; the Canadian Institutes of Health Research (CIHR) and the Accelerating Clinical Trials Consortium Canada (ACTAEC); the University Medical Center (UMC) Utrecht and ZonMW in the Netherlands; the Health Research Council of New Zealand (HRC) and the Starship Foundation in New Zealand; the National Healthcare Group Fund and National Medical Research Council (NMRC) in Singapore; the National Institute for Health and Care Research (NIHR) in the UK; and the Paterson Family Foundation supported activities in South Africa.
Collaboration: The SNAP platform trial is led by researchers at the Doherty Institute (a joint venture between the University of Melbourne and the Royal Melbourne Hospital) and the University of Newcastle. The trial is the result of an international consortium with the Doherty Institute (Australia), Aotearoa Clinical Trials (New Zealand), the European Clinical Research Alliance on Infectious Diseases (ECRAID Netherlands), the Research Institute of the McGill University Health Centre (The Institute, Canada), University College London Innovative Clinical Trials Unit (UK), The University Medical Center Utrecht (Netherlands), the Clinical Health Research Unit (CHRU, South Africa), Tan Tock Seng Hospital (TTSH, Singapore), and Rambam Health Corporation, The Sheba Fund for Health Services and Research and Beilinson Hospital (Israel).
About the Peter Doherty Institute for Infection and Immunity
Finding solutions to prevent, treat and cure infectious diseases and understanding the complexities of the immune system requires innovative approaches and concentrated effort. This is why The University of Melbourne – a world leader in education, teaching and research excellence – and The Royal Melbourne Hospital – an internationally renowned institution providing outstanding care, treatment and medical research – have partnered to create the Peter Doherty Institute for Infection and Immunity (Doherty Institute); a centre of excellence where leading scientists and clinicians collaborate to improve human health globally. doherty.edu.au
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