Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/19906
Título
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
Autor(es)
Blanco-Martín, Tania | Alonso-García, Isaac | González-Pinto, Lucía | Outeda-García, Michelle | Guijarro-Sánchez, Paula | López-Hernández, Inmaculada | Perez-Vazquez, Maria ISCIII | Aracil, Belen ISCIII | López-Cerero, Lorena | Fraile-Ribot, Pablo | Oliver, Antonio | Vázquez-Ucha, Juan Carlos | Beceiro, Alejandro | Bou, Germán | Arca-Suárez, Jorge | GEMARA/SEIMC-CIBERINFEC Study Group on the activity and resistance mechanisms to new β-lactams and β-lactamase inhibitors (PROTECT)
Fecha de publicación
2024-05
Cita
Int J Antimicrob Agents. 2024 May;63(5):107150.
Idioma
Inglés
Tipo de documento
research article
Resumen
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.
Palabras clave
β-lactamases | Cefiderocol | β-lactam/β-lactamase inhibitor | Combinations | Permeability | Double-carbapenemase | Escherichia coli
MESH
Escherichia coli | beta-Lactamases | Cephalosporins | Microbial Sensitivity Tests | beta-Lactamase Inhibitors | Azabicyclo Compounds | Anti-Bacterial Agents | Drug Combinations | Cyclooctanes | Cefiderocol | Ceftazidime | Cefepime | Borinic Acids | Carboxylic Acids | Lactams | Triazoles | Boronic Acids | Meropenem | Aztreonam | Imipenem | Bacterial Proteins | Heterocyclic Compounds, 1-Ring | Cell Membrane Permeability
Versión en línea
DOI
Aparece en las colecciones
- Investigación > IIS > IdisBa - Instituto de Investigación Sanitaria Illes Balears (Baleares)
- Investigación > ISCIII > Centro Nacional de Microbiología (CNM)
- Investigación > IIS > IBIS - Instituto de Biomedicina de Sevilla (Andalucía)
- Investigación > IIS > INIBIC - Instituto de Investigación Biomédica A Coruña (Galicia)
Ficheros en el ítem
- Nombre:
- ActivityCefiderocolInnovativeB ...
- Tamaño:
- 611.6Kb
- Formato:
- Descripción:
- Articulo
- Nombre:
- Supplementary1_ActivityCefider ...
- Tamaño:
- 599.9Kb
- Formato:
- Descripción:
- supplementary material 1
- Nombre:
- Supplementary2_ActivityCefider ...
- Tamaño:
- 218.0Kb
- Formato:
- Descripción:
- supplementary material 2
Este Item está sujeto a una licencia Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Ítems relacionados
Mostrando ítems relacionados por Título, autor o palabras clave.
-
2023-06
research article
Lopez-Siles, Mireia ISCIII; Moure García, Zaira ISCIII; Muadica, Aly Salimo ISCIII; et al.