Résumé
Cefiderocol is a recently developed siderophore cephalosporin with activity on various multidrug-resistant (MDR) Gram-negative bacilli (GNB), including those producing Ambler class A, B and D carbapenemases. The objectives of TROJAN-BMR study were i) to compare in vitro activity of Cefiderocol with that of other last-resort antibiotics against a collection of well characterized MDR Enterobacterales and Pseudomonas aeruginosa strains isolated in South of France, and ii) to evaluate the performance of Cefiderocol antimicrobial susceptibility testing (AST) available methods. The collection of strains included 127 Enterobacterales from various clones of which 119 were carbapenemase producers (93.7%) and 53 MDR P. aeruginosa of which 6 produced a metallo-β-lactamase (11.3%). The minimum inhibitory concentrations (MICs) of Cefiderocol was determined using UMIC® broth microdilution method (BMD), and comparators MICs were measured by BMD using the SensititreTM EUMDRXXF plate and with the recently marketed strips from Liofilchem for aztreonam-avibactam. The results of AST were interpreted according to EUCAST breakpoints for all antimicrobial agents. CLSI breakpoints were also used for Cefiderocol. Performance of ComASP® broth microdilution (BMD) and disc diffusion on two different Mueller-Hinton (MH) media from Bio-Rad and BD were determined according to ISO 20776-2:2007. UMIC® BMD was considered as the reference method to determine Cefiderocol MICs. Cefiderocol showed overall potent in vitro activity on Enterobacterales (81.9% susceptible, S) and MDR P. aeruginosa (84.9% S) using EUCAST breakpoints. Activity on NDM-producing isolates was comparable to that described in the literature (79.3% S). Among Enterobacterales, the most effective comparators were colistin, aztreonam-avibactam, meropenem-vaborbactam and amikacin with susceptibility rates of 99.2%, 92.9%, 85%, and 76.4% respectively.Concerning P. aeruginosa, only colistin had a better susceptibility rate than Cefiderocol (100%). The disc diffusion method showed better performance on BD MH agar than Bio-Rad. The ComASP® method did not provide sufficient performance to be considered a reliable method.Cefiderocol was highly active on a large collection of MDR GNB including high-risk clones. Susceptibility to this last-resort antibiotic must be assessed using a validated method when clinical use is considered.