SNAP Trial Reports Cefazolin Safety And Effectiveness In MSSA Bacteremia

Key Takeaways

• Cefazolin was reported to perform at least as well as cloxacillin or flucloxacillin for MSSA bacteremia.
• Cefazolin was associated with fewer side effects and fewer cases of acute kidney injury in the reported comparison.
• The findings were presented as support for moving away from cloxacillin as the default treatment, with uptake tied to hospitals, laboratories, and guideline groups.

For methicillin-susceptible Staphylococcus aureus bloodstream infection, 90-day mortality was 15% with cefazolin and 17% with flucloxacillin in the SNAP Trial. Cefazolin was described as at least as effective as cloxacillin or flucloxacillin for MSSA bloodstream infection and was associated with fewer adverse events in this comparison. The analysis centered on bloodstream infection rather than broader staphylococcal disease categories. Overall, the findings paired similar effectiveness with a safety advantage.

A June 18, 2026 McGill University Health Centre SNAP Trial summary presented these results from the international SNAP Trial. The institutional report said related papers appeared simultaneously in the New England Journal of Medicine and The Lancet on June 17. It also described SNAP as the world’s largest study undertaken to improve treatment for Staphylococcus aureus infections. In this setting, flucloxacillin was the comparator name used in many countries, while cloxacillin remained the default frame in the report. The clinical focus then returned to cefazolin versus cloxacillin for MSSA bloodstream infection.

In the safety findings, acute kidney injury occurred in 14% of patients receiving cefazolin and 20% of those receiving flucloxacillin. Cefazolin was also described as having fewer side effects overall within the MSSA comparison. The investigators also cited an 89% probability that cefazolin was associated with lower mortality, without repeating the primary mortality comparison. These details kept the emphasis on tolerability rather than any tradeoff in effectiveness. The kidney injury difference favored cefazolin on this renal safety measure.

The investigators said these findings support moving away from cloxacillin as the default treatment for MSSA and PSSA infections. They also said implementation will depend on hospitals, laboratories, and guideline groups incorporating the evidence into clinical care. In attributed commentary, a SNAP investigator said cefazolin should be considered the first-line option for MSSA bloodstream infection. The report also noted that cefazolin availability may need to increase in some countries. It also referenced a related Lancet study evaluating benzylpenicillin for penicillin-susceptible Staphylococcus aureus bacteraemia, broadening the framing of beta-lactam choices across susceptible bloodstream infections.