TROJAN-MDR: in vitro activity of cefiderocol and comparators against multidrug-resistant Enterobacterales and Pseudomonas aeruginosa strains in Southern France, evaluation of available testing methods performances.

Abstract

Background:  Cefiderocol, a newly introduced siderophore cephalosporin, exhibits activity against various multidrug-resistant (MDR) Gram-negative bacilli (GNB), including producers of Ambler class A, B and D carbapenemases. The TROJAN-MDR study aimed to (i) compare the in vitro activity of cefiderocol with other last-resort antibiotics against a well-characterized collection of Enterobacterales and Pseudomonas aeruginosa strains from Southern France, and (ii) assess the performance of available cefiderocol antimicrobial susceptibility testing (AST) methods.

Methods: The collection comprised 127 Enterobacterales from various clones, including 119 carbapenemase producers (93.7%), and 53 MDR P. aeruginosa. The minimum inhibitory concentrations (MICs) of cefiderocol were determined using the UMIC^® broth microdilution method (BMD) as the reference. Comparators MICs were measured using Sensititre™ EUMDRXXF plates and Liofilchem strips for aztreonam-avibactam. Results were interpreted according to EUCAST breakpoints, with CLSI breakpoints also used for cefiderocol. The performance of the ComASP^® BMD and disk diffusion on two different Mueller-Hinton media (Bio-Rad and BD) were evaluated according to ISO 20776-2:2007 and 2021.

Results: Cefiderocol demonstrated potent activity on Enterobacterales (81.9% susceptible) and P. aeruginosa (84.9%) using EUCAST breakpoints. Among Enterobacterales, the most effective comparators were colistin, aztreonam-avibactam, meropenem-vaborbactam, and amikacin, with susceptibility rates of 99.2%, 98.4%, 85%, and 76.4%, respectively. For P. aeruginosa, only colistin exhibited better activity (100%). The disk diffusion method showed superior performance on BD medium compared to Bio-Rad. The ComASP^® method did not provide sufficient performance to be considered reliable.

Conclusions: Cefiderocol was highly active against a large collection of MDR GNB, including high-risk clones. It is crucial to assess susceptibility to this last-resort antibiotic using a validated method when considering clinical use.