Non-inferiority Trial Comparing Cloxacillin vs Cefazolin in Methicillin-susceptible Staphylococcus Aureus Bacteremia

Summary

"Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia remains a major cause of community- or hospital-acquired bloodstream infections with an overall mortality estimated around 25%. Anti-staphylococcal penicillins (APs) such as oxacillin or cloxacillin are recommended as first-line agents. With the exception of first-generation cephalosporin (1GC) such as cefazolin, no alternative has yet proven a similar efficacy. Due to an unfavourable safety profile for high doses used in severe infection, an uneasy dosing schedule in patients with renal failure and possible recurrent stock-out events for APs, alternative to APs are needed. This led to propose an open-label, randomized, controlled parallel groups, phase IV, non-inferiority trial comparing the efficacy, the safety, and the ecological impact of cefazolin versus cloxacillin for the treatment of MSSA bacteremia in adults. The primary objective is to compare the therapeutic efficacy of cefazolin vs cloxacillin at day 90 after the inclusion. "

Timeline

Start

2018-09-05

Primary completion

2024-02-22

Completion

2025-03-10

Publications

• Results Burdet C, Saidani N, Dupieux C, Lemaignen A, Canoui E, Surgers L, Vareil MO, Lefort A, Lepeule R, Peiffer-Smadja N, Charmillon A, Le Moing V, Boutoille D, Tolsma V, Abgrall S, Wolff M, Tattevin P, Esposito-Farese M, Vandenesch F, Duval X, Tubiana S, Lescure FX; CloCeBa Study Group. Cloxacillin versus cefazolin for meticillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): a prospective, open-label, multicentre, non-inferiority, randomised clinical trial. Lancet. 2025 Nov 15;406(10517):2349-2359. doi: 10.1016/S0140-6736(25)01624-1. Epub 2025 Oct 17.
• Burdet C, Loubet P, Le Moing V, Vindrios W, Esposito-Farese M, Linard M, Ferry T, Massias L, Tattevin P, Wolff M, Vandenesch F, Grall N, Quintin C, Mentre F, Duval X, Lescure FX; CloCeBa study group. Efficacy of cloxacillin versus cefazolin for methicillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): study protocol for a randomised, controlled, non-inferiority trial. BMJ Open. 2018 Sep 1;8(8):e023151. doi: 10.1136/bmjopen-2018-023151.

Drugs

Indications