OBJECTIVES: Pseudomonas aeruginosa is a major causative agent of hospital infections. The purpose of this study was to determine the antibiotic susceptibility of P. aeruginosa in a French multicentre study and to investigate the mechanisms of beta-lactam resistance. METHODS: Four hundred and fifty non-repetitive strains of P. aeruginosa were collected in 15 French university hospitals in 2004. MICs of antibiotics were measured by agar dilution methods. For all the strains with MICs of ticarcillin >16 mg/L, detection and identification of the beta-lactamases, quantitative determination of cephalosporinase and overproduction of the MexAB-OprM efflux pump were evaluated. RESULTS: The percentages of susceptible isolates were as follows: ticarcillin, 62%; ticarcillin + clavulanic acid, 61%; piperacillin, 78%; piperacillin + tazobactam, 80% (MICs