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. 2024 Oct 24;6(5):dlae169.
doi: 10.1093/jacamr/dlae169. eCollection 2024 Oct.

Real-world performance of susceptibility testing for cefiderocol: insights from a prospective multicentre study on Gram-negative bacteria

Alvaro Irigoyen-von-Sierakowski  1 , Azahara Ocaña  1 , Rosa Sánchez-Mayoral  1 , Emilia Cercenado  1 ; GEIRAS-SEIMC Study Group
Collaborators, Affiliations

Real-world performance of susceptibility testing for cefiderocol: insights from a prospective multicentre study on Gram-negative bacteria

Alvaro Irigoyen-von-Sierakowski et al. JAC Antimicrob Resist. .

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.

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Figures

Figure 1.
Figure 1.
Distribution of inhibition zone diameter [30 μg discs (Liofilchem, Italy)] according to the MIC (mg/L) determined by ComASP® cefiderocol panels (Liofilchem, Italy) for Enterobacterales. The coloured bars represent susceptible and resistant strains; the discontinuous vertical line marks the EUCAST zone diameter breakpoints (23 mm).
Figure 2.
Figure 2.
Distribution of inhibition zone diameter [30 μg discs (Liofilchem, Italy)] according to the MIC (mg/L) determined by ComASP® cefiderocol panels (Liofilchem, Italy) for P. aeruginosa, Acinetobacter spp. and S. maltophilia. The coloured bars represent susceptible and resistant strains; the discontinuous vertical line marks the EUCAST zone diameter breakpoints (22 mm for P. aeruginosa and 17 and 20 mm PK–PD breakpoints for Acinetobacter spp. and S. maltophilia, respectively).
See this image and copyright information in PMC

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