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Activity of cefiderocol and innovative β-lactam/β-lactamase inhibitor combinations against isogenic strains of Escherichia coli expressing single and double β-lactamases under high and low permeability conditions.

Author information

Affiliations

  • 1. Servicio de Microbiología and Instituto de Investigación Biomédica A Coruña (INIBIC), Complexo Hospitalario Universitario A Coruña, A Coruña, Spain.
      Authors
    • Blanco-Martín T 1
    • Alonso-García I 1
    • González-Pinto L 1
    • Outeda-García M 1
    • Guijarro-Sánchez P 1
    (5 authors)
  • 2. Laboratorio de Referencia para tipado molecular y detección de mecanismos de resistencia a antimicrobianos de Andalucía (PIRASOA). Unidad de Gestión Clínica de Microbiología y Enfermedades Infecciosas, Hospital Universitario Virgen Macarena, Sevilla. Instituto de Biomedicina de Sevilla (IBIS), CSIC, Universidad de Sevilla, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
      Authors
    • López-Hernández I 2
    • López-Cerero L 2
    (2 authors)
  • 3. Laboratorio de Referencia e Investigación en Resistencia a Antibióticos e Infecciones relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
      Authors
    • Pérez-Vázquez M 3
    • Aracil B 3
    (2 authors)
  • 4. Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases e Instituto de Investigación Sanitaria Illes Balears (IDISBA), Palma de Mallorca, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
      Authors
    • Fraile-Ribot P 4
    • Oliver A 4
    (2 authors)
  • 5. Servicio de Microbiología and Instituto de Investigación Biomédica A Coruña (INIBIC), Complexo Hospitalario Universitario A Coruña, A Coruña, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
      Authors
    • Vázquez-Ucha JC 5
    • Beceiro A 5
    • Bou G 5
    • Arca-Suárez J 5
    (4 authors)

ORCIDs linked to this article

International Journal of Antimicrobial Agents, 19 Mar 2024, 63(5):107150
https://doi.org/10.1016/j.ijantimicag.2024.107150 PMID: 38513748 

This article has been corrected. See Int J Antimicrob Agents. 2024 Jul 8:107264. doi: 10.1016/j.ijantimicag.2024.107264.

Abstract 

Objectives

To analyse the impact of the most clinically relevant β-lactamases and their interplay with low outer membrane permeability on the activity of cefiderocol, ceftazidime/avibactam, aztreonam/avibactam, cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, imipenem/relebactam, meropenem/vaborbactam, meropenem/xeruborbactam and meropenem/nacubactam against recombinant Escherichia coli strains.

Methods

We constructed 82 E. coli laboratory transformants expressing the main β-lactamases circulating in Enterobacterales (70 expressing single β-lactamase and 12 producing double carbapenemase) under high (E. coli TG1) and low (E. coli HB4) permeability conditions. Antimicrobial susceptibility testing was determined by reference broth microdilution.

Results

Aztreonam/avibactam, cefepime/zidebactam, cefiderocol, meropenem/xeruborbactam and meropenem/nacubactam were active against all E. coli TG1 transformants. Imipenem/relebactam, meropenem/vaborbactam, cefepime/taniborbactam and cefepime/enmetazobactam were also highly active, but unstable against most of MBL-producing transformants. Combination of β-lactamases with porin deficiency (E. coli HB4) did not significantly affect the activity of aztreonam/avibactam, cefepime/zidebactam, cefiderocol or meropenem/nacubactam, but limited the effectiveness of the rest of carbapenem- and cefepime-based combinations. Double-carbapenemase production resulted in the loss of activity of most of the compounds tested, an effect particularly evident for those E. coli HB4 transformants in which MBLs were present.

Conclusions

Our findings highlight the promising activity that cefiderocol and new β-lactam/β-lactamase inhibitors have against recombinant E. coli strains expressing widespread β-lactamases, including when these are combined with low permeability or other enzymes. Aztreonam/avibactam, cefiderocol, cefepime/zidebactam and meropenem/nacubactam will help to mitigate to some extent the urgency of new compounds able to resist MBL action, although NDM enzymes represent a growing challenge against which drug development efforts are still needed.

Full text links 

Read article at publisher's site: https://doi.org/10.1016/j.ijantimicag.2024.107150

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Funding 

Funders who supported this work.

CIBERINFEC

    Instituto de Salud Carlos III

      Xunta de Galicia