Real-world performance of susceptibility testing for cefiderocol: insights from a prospective multicentre study on Gram-negative bacteria
Authors: Irigoyen-von-Sierakowski Alvaro , Ocaña Azahara , Sánchez-Mayoral Rosa , Cercenado Emilia ,   GEIRAS-SEIMC Study Group, Fernández Javier , López Ana , Villuendas Cruz , Arias Antonina , Manuel García-Lechuz Juan , Cameo Mª Isabel , González Carlos , Merino Pilar , Rodríguez-Avial Icíar , Viedma Esther , Megías Gregoria , Ortega Mª Pilar , Pitart Cristina , Colmenarejo Cristina , Fernández Marina , Alonso Marta , Torralba Ana , Pérez Felipe , Camacho Pablo , Guerrero Carmen , Sáinz de Baranda Caridad , Fidalgo Berta , Sampere Ángeles , Hernando Noelia , Galán Fátima , Paredes Sonia , Goncalves Lisbeth , Rodríguez María , Fuster Carlos , Mulet Xavier , Fernández Mª Carmen , Bou Germán , Guzmán Julia , Quesada Mª Dolores , Wang Jun Hao , Navarro David , Garau Margarita , Díaz Paz , Gallegos Mª Carmen , Martínez Mariela , Rodríguez Ángel , López Isabel Cristina , Asensio Mª Luz , Portillo Mª Eugenia , Oteiza Amaya , Pedro Amparo San , Yagüe Genoveva , Gil Yolanda , Barrado Laura , Pérez Mª Teresa , Pérez Patricia , Ortiz de la Tabla Victoria , Gimeno Concepción , Tormo Nuria , Sánchez Antonia , Martí Paula , Martín Ana , Floren Laura , Chamizo Francisco Javier , García María , Cordero Desirée , de la Iglesia Pedro , Giner Salvador , López-Hontangas José Luis , Sánchez-Romero Isabel , Barrios José Luis , Rivera Alba , Tubau Fe , Gutiérrez Nieves , García-Garrote Fernando , Calvo Jorge , Siller María , Seral Cristina , Coira Amparo , Garduño Eugenio , Vasallo Francisco José , Padilla Emma , Viñado Belén , Collazos Ana , Simón María , Semiglia Mª Auxiliadora , Alarcón Teresa , Díez María , Domingo Diego , Ramón Susana , Jiménez Gemma , García Mª Victoria , Puente Lucía , Leal Álvaro , Irigoyen-von-Sierakowski Alvaro , Ocaña Azahara , Sánchez-Mayoral Rosa , Cercenado Emilia 
Published: October 2024

Abstract

Objectives
Cefiderocol is a novel siderophore-conjugated cephalosporin developed for the treatment of multidrug-resistant Gram-negative bacterial (GNB) infections. However, the current gold standard for cefiderocol susceptibility testing, broth microdilution (BMD) using iron-depleted cation-adjusted Mueller–Hinton broth, presents challenges for many microbiology laboratories. In this study, we evaluate the real-world performance of disc diffusion (DD) and a commercial BMD method (ComASP®) to test cefiderocol susceptibility in a series of isolates collected prospectively from severely ill patients in a multicentre study.

Methods
The susceptibilities of 1472 isolates (632 Enterobacterales, 532 Pseudomonas aeruginosa, 84 Acinetobacter spp. and 224 Stenotrophomonas maltophilia) collected in 60 Spanish hospitals were analysed following the EUCAST 2023 and 2024 criteria. We assessed the performance of DD (cefiderocol 30 μg disc, Liofilchem) and a commercial BMD method (ComASP® Cefiderocol, Liofilchem).

Results
A total of 1408 and 1450 isolates were susceptible by DD and ComASP® BMD, respectively. Overall, the agreement between both methods was 96.9%. Forty-four isolates were resistant by DD but susceptible by ComASP® BMD, and two were susceptible by DD but resistant by ComASP® BMD (Acinetobacter baumannii isolates). Adoption of the updated 2024 EUCAST DD breakpoints and areas of technical uncertainty (ATUs) led to a decrease in susceptibility among Enterobacterales (95.3% versus 92.6%).

Conclusions
DD is a straightforward, rapid and accessible method for routine determination of cefiderocol susceptibility in real-world practice. ComASP® BMD shows a high agreement with DD in susceptible isolates and may help to resolve DD interpretability concerns in isolates with susceptibility results within the ATU, but caution is warranted when testing resistant isolates.