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Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
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Cefiderocol activity against multidrug-resistant isolates from the PERSEUS study: relationship between cefiderocol

Rafael Cantón1,2, María García-Castillo1,2, Marta Hernández-García1,2

  • 1Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.

The Journal of Antimicrobial Chemotherapy
|May 26, 2026
PubMed
Abstract

Insights

Cefiderocol shows 86% susceptibility against MDR Gram-negative infections, particularly Pseudomonas aeruginosa. Clinical cure was observed even with resistant isolates, suggesting further research into resistance mechanisms and standardized testing is needed.

Area of Science:

  • Infectious Diseases
  • Microbiology
  • Pharmacology

Background:

  • Multidrug-resistant (MDR) Gram-negative infections pose a significant global health threat.
  • Cefiderocol is a novel antibiotic with activity against MDR Gram-negative pathogens.
  • The PERSEUS study evaluated cefiderocol's efficacy in Spain.

Purpose of the Study:

  • To microbiologically evaluate cefiderocol susceptibility in MDR Gram-negative isolates from the PERSEUS study.
  • To correlate microbiological findings with clinical outcomes in patients treated with cefiderocol.
  • To assess the performance of different susceptibility testing methods for cefiderocol.

Main Methods:

  • Retrospective analysis of 57 MDR Gram-negative isolates from the PERSEUS study.
  • Cefiderocol susceptibility testing using broth microdilution (BMD), commercial BMD panels, MIC strips, and disk diffusion (EUCAST 2024 criteria).
  • Whole genome sequencing (WGS) to identify resistance genes (e.g., β-lactamases) and mutations; review of patient clinical charts.

Main Results:

  • Pseudomonas aeruginosa accounted for 72% of isolates.
  • Overall cefiderocol susceptibility was 86%, superior to most comparators except colistin.
  • Commercial BMD methods showed high concordance with reference testing.
  • Resistant isolates frequently harbored metallo-β-lactamases and mutations in iron transport genes.
  • Clinical cure occurred in some patients with cefiderocol-resistant isolates, indicating MIC may not always predict clinical failure.

Conclusions:

  • Standardized susceptibility testing and genotype-phenotype correlation studies are crucial for cefiderocol use.
  • Cefiderocol is a promising treatment for MDR Gram-negative infections, especially P. aeruginosa.
  • Validated testing methods and surveillance are essential for clinical adoption.

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