In vivo efficacy of cefiderocol against ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa carrying the AmpC E219K substitution
ABSTRACT Chromosomal AmpC variants selected during ceftolozane/tazobactam or ceftazidime/avibactam therapy may affect cefiderocol activity. We evaluated the impact of the E219K substitution on cefiderocol efficacy using isogenic Pseudomonas aeruginosa pairs in a murine bacteremia model. Cefiderocol achieved greater bacterial reductions in parental isolates than in E219K derivatives, despite susceptible MICs. Cefiderocol failed to achieve stasis against a cefiderocol-resistant isolate. E219K impaired cefiderocol efficacy in vivo , supporting close monitoring of cefiderocol activity against isolates carrying this variant.
Authors
- Pablo A. Fraile-Ribot (ORCID: https://orcid.org/0000-0002-3822-9965)
- Biel Taltavull (ORCID: https://orcid.org/0009-0006-3452-8665)
- Michelle Outeda-García (ORCID: https://orcid.org/0000-0002-6737-0239)
- Juan Carlos Vázquez-Ucha (ORCID: https://orcid.org/0000-0003-4949-0779)
- Alejandro Beceiro (ORCID: https://orcid.org/0000-0002-6340-7815)
- Antonio Oliver (ORCID: https://orcid.org/0000-0001-9327-1894)
- Andrea Muras (ORCID: https://orcid.org/0000-0003-1603-9762)
- Jorge Arca-Suárez (ORCID: https://orcid.org/0000-0002-4248-503X)
- Paula Guijarro-Sánchez (ORCID: https://orcid.org/0000-0002-8456-0085)
- Isaac Alonso-García (ORCID: https://orcid.org/0000-0002-1681-969X)
- Germán Bou (ORCID: https://orcid.org/0000-0001-8837-0062)
- Lucía González-Pinto (ORCID: https://orcid.org/0000-0002-8387-3784)
- Arianna Rodríguez-Coello (ORCID: https://orcid.org/0009-0007-5066-3020)
- Andrea García-Pose
- Gabriela A. Báez-Barroso (ORCID: https://orcid.org/0009-0003-1042-8174)
Institutions
- Universidade da Coruña (ES)
- Instituto de Salud Carlos III (ES)
- Health Research Institute of the Balearic Islands (ES)
- Complexo Hospitalario Universitario A Coruña (ES)
- Hospital Universitario Son Espases (ES)
- Instituto de Investigación Biomédica de A Coruña (ES)
Publication Details
- Journal
- Antimicrobial Agents and Chemotherapy
- Published
- 2026-09-16
- DOI
- https://doi.org/10.1128/aac.00724-26
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 0.00