Cloxacillin versus cefazolin for meticillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): a prospective, open-label, multicentre, non-inferiority, randomised clinical trial.

Summary

In a multicentre open-label non-inferiority RCT (n=315 randomized; 292 analyzed), cefazolin achieved the 90-day composite primary endpoint at a similar rate to cloxacillin (75% vs 74%; non-inferiority p=0.012). Serious adverse events and acute kidney injury were significantly less frequent with cefazolin.

Key Findings

• Primary composite endpoint met in 75% (cefazolin) vs 74% (cloxacillin); treatment difference −1% (95% CI −11 to 9); non-inferiority p=0.012.
• Serious adverse events: 15% with cefazolin vs 27% with cloxacillin (p=0.010).
• Acute kidney injury: 1% with cefazolin (1/134) vs 12% with cloxacillin (15/128) (p=0.0002).
• Randomization stratified by vascular-access-associated bacteraemia and center; total treatment ≥14 days.

Clinical Implications

Cefazolin can be adopted as a first-line parenteral therapy for MSSA bacteraemia (excluding CNS/device infections), offering comparable efficacy with reduced risk of acute kidney injury and better tolerability.

Limitations

• Open-label design may introduce performance and detection bias.
• Excluded patients with intravascular implants or suspected CNS infection, limiting generalizability.
• Conducted in France; antimicrobial practices may vary internationally.

Future Directions

Evaluate cefazolin in endocarditis and device-related infections, assess outpatient parenteral therapy feasibility, and perform cost-effectiveness and stewardship impact analyses.