Global SNAP Trial Finds Cefazolin Safer and Equally Effective as Flucloxacillin for MSSA Bloodstream Infections

A landmark international clinical trial has upended decades of treatment dogma for one of the world's deadliest bloodstream infections. The Staphylococcus aureus Network Adaptive Platform (SNAP) trial—the largest randomized study ever conducted for S. aureus bloodstream infections—has demonstrated that cefazolin查看药品详情 is at least as effective as, and significantly safer than, flucloxacillin查看药品详情 (cloxacillin), the long-standing standard of care for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia.

The findings, published in the New England Journal of Medicine on June 17, provide the clearest evidence to date that cefazolin查看药品详情 should become the new first-line treatment for most adults with this life-threatening infection.

A Global Research Effort

The SNAP trial compared cefazolin查看药品详情 and flucloxacillin查看药品详情 in 1,341 patients with S. aureus bloodstream infections across eight countries, including the Netherlands, Canada, Australia, and the United Kingdom. In the Netherlands, the study was coordinated by UMC Utrecht查看公司主页, Radboudumc查看公司主页, and Ecraid, with Radboudumc researchers receiving a ZonMw查看公司主页 grant in 2022 that enabled Dutch participation.

"International trials like SNAP help ensure that the results are reliable, broadly applicable and capable of changing care on a global scale," said Dr. Todd Lee, co-lead investigator, scientist in the Infectious Diseases and Immunity in Global Health Program at the Research Institute of the McGill University Health Centre查看公司主页, and Professor at McGill University.

Superior Safety with Comparable Efficacy

The results were striking. Fifteen percent of patients who received cefazolin查看药品详情 died within 90 days, compared with 17 percent of those who received flucloxacillin查看药品详情. More notably, cefazolin was associated with substantially fewer cases of acute kidney injury (搜索)搜索该疾病—a serious complication that can occur during sepsis or its treatment—at 14 percent versus 20 percent with flucloxacillin.

Professor Steven Tong, an infectious diseases physician at the Peter Doherty Institute for Infection and Immunity and global co-lead investigator of the SNAP Trial, noted: "In the treatment of MSSA infections, there is an 89 percent probability that cefazolin查看药品详情 is associated with lower mortality. Patients treated with cefazolin fare better."

"The results are sufficiently compelling that I immediately made the switch in my own clinical practice," Professor Tong added.

Challenging Long-Held Assumptions

For decades, flucloxacillin查看药品详情 has been the preferred treatment in countries such as the Netherlands, whereas cefazolin查看药品详情 has been the first-line choice in nations including the United States. Until now, no large randomized trial had directly compared the two drugs.

"For decades, we have not known the best way to treat this serious infection which affects hundreds of thousands of patients worldwide. We were taught that cloxacillin was better based on expert opinion and in vitro data. So it is critical that we now have randomized data that teaches us this thinking was not correct," said Dr. Lee.

Infectious disease specialist Marjolein Hensgens of UMC Utrecht查看公司主页 reinforced this view: "The results show that patients treated with cefazolin查看药品详情 do just as well as—and possibly even better than—those treated with flucloxacillin查看药品详情. Moreover, treatment with cefazolin is associated with significantly fewer side effects."

A New Standard of Care

Medical microbiologist Marc Bonten of UMC Utrecht查看公司主页 described the trial as a major step forward: "The SNAP study is a major step forward, not only because of what it teaches us about patient care, but also because it demonstrates the power of international collaboration in answering questions that have challenged us for decades. For the first time, we have randomized clinical trial evidence to guide the treatment of severe staphylococcal infections. These results support cefazolin查看药品详情 becoming the new standard treatment for most adults with this type of infection."

The SNAP trial is an ongoing platform trial designed to evaluate multiple treatment strategies simultaneously. To date, more than 6,000 patients have participated, enrolled at more than 130 hospitals across Australia, Canada, Germany, Israel, the Netherlands, New Zealand, Singapore, South Africa, Sweden, France, Spain, and the United Kingdom.

Dutch Sub-Studies and Future Directions

Radboudumc查看公司主页 is leading two Dutch sub-studies coordinated by PhD candidate Fleur Sinkeler, investigating drug exposure, effectiveness, side effects, and differences in resistance between cefazolin查看药品详情 and flucloxacillin查看药品详情. Principal investigator and hospital pharmacist-clinical pharmacologist Nynke Jager stated: "Cefazolin is therefore safer and equally effective as flucloxacillin. To further optimize treatment, we are collecting information on drug exposure, effectiveness, and adverse effects. We are also investigating differences in resistance between flucloxacillin and cefazolin. With this information, we hope to provide even better, more personalized treatment in the future."

The Burden of S. aureus Bloodstream Infections

Staphylococcus aureus is a major cause of life-threatening bloodstream infections, responsible for approximately 300,000 deaths worldwide each year. In the Netherlands alone, despite the best possible care, two to three patients die every day as a result of such infections. The most serious form carries a mortality rate of 15 to 25 percent.

Translating Evidence into Practice

Researchers acknowledge that the next challenge will be translating these findings into routine clinical practice. While cefazolin查看药品详情 availability may need to increase in some countries, implementation will ultimately depend on hospitals, laboratories, and guideline groups incorporating the findings into clinical care.

"Trials generate the evidence, but the next step is making sure that evidence changes practice," said Dr. Lee.

The SNAP component for which the current results have been reported, as well as the Dutch sub-studies, are funded by ZonMw查看公司主页's Good Use of Medicines programme and UMC Utrecht查看公司主页. Ten hospitals in the Netherlands currently participate in the study.