Real-world performance of susceptibility testing for cefiderocol: insights from a prospective multicentre study on Gram-negative bacteria
Álvaro Irigoyen, Azahara Ocaña, Rosa Sánchez-Mayoral, Emilia Cercenado, GEIRAS-SEIMC Study Group, Javier Fernández, Ana López, Cruz Villuendas, Antonina Arias, Juan Manuel García-Lechuz, María Isabel Cameo, Carlos González, P. Merino, Iciar Rodríguez-Avial, Esther Viedma, Gregoria Megías, Ma Pilar Ortega, Cristina Pitart, Cristina Colmenarejo, Marina Fernández, Marta Alonso, Ana Torralba, Felipe Pérez, Pablo Camacho, Carmen Guerrero, Caridad Sainz de Baranda, Berta Fidalgo, Ángeles Sampere, Noelia Hernando, Fátima Galán‐Sánchez, Sonia Paredes, Lisbeth Goncalves, Maria Pilar Rodríguez, Carlos Fuster, Xavier Mulet, M. Carmen Fernández‐Santaella, Germán Bou, J A Antonio Guzmán, Ma Dolores Quesada, Jun Hao Wang-Wang, David Navarro, Margarita Garau, Paz Díaz, Maria Belen Rojas Gallegos, Mariela Martínez, Ángel Rodríguez, Isabel Cristina Buriticá López, Margarita Asensio, María Eugenia Portillo, Amaya C. Oteiza, Antônio Pedro, Genoveva Yagüe, Yolanda Gil, Laura Barrado, Marı́a del Carmen Pérez, Patricia Pérez, Victoria Ortiz de la Tabla, Concepción Gimeno, Nuria Tormo, Antonia Víñez Sánchez, Paula Martí, Ana Martín, Laura Florén-Zabala, Francisco Javier Chamizo-López, M. B. Mora Garcia, Desirée Cordero, Pedro de la Iglesia, Salvador Giner, José Luís López-Hontangas, Isabel Sánchez‐Romero, José Luís González Barrios, Alba Rivera, Fé Tubau, Nieves Gutiérrez, Fernando Garcı́a-Garrote, J. H. Calvo, María Siller, Cristina Seral, Amparo Coira, Eugenio Garduño, Francisco J. Vasallo, Emma Padilla, Belén Viñado, Ana Collazos, Marı́a Rosa Simón, Ma Auxiliadora Semiglia, Teresa Alarcón, María José Díez, Diego Domingo, Susana Sánchez Ramón, Gemma Jiménez, Ma Victoria García, L. Sánchez de la Puente, Álvaro Leal, Álvaro Irigoyen, Azahara Ocaña, Rosa Sánchez-Mayoral, Emilia Cercenado
Abstract
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.