2026-04-29T14:03:48Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/199062025-02-05T11:59:15Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16958col_20.500.12105_16967col_20.500.12105_16985
Repisalud
author
Blanco-Martín, Tania
author
Alonso-García, Isaac
author
González-Pinto, Lucía
author
Outeda-García, Michelle
author
Guijarro-Sánchez, Paula
author
López-Hernández, Inmaculada
author
Perez-Vazquez, Maria
author
Aracil, Belen
author
López-Cerero, Lorena
author
Fraile-Ribot, Pablo
author
Oliver, Antonio
author
Vázquez-Ucha, Juan Carlos
author
Beceiro, Alejandro
author
Bou, Germán
author
Arca-Suárez, Jorge
author
GEMARA/SEIMC-CIBERINFEC Study Group on the activity and resistance mechanisms to new β-lactams and β-lactamase inhibitors (PROTECT)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Merck, Sharp & Dohme
funder
Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
funder
RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España)
funder
Plan Nacional de I+D+i (España)
funder
Xunta de Galicia (España)
funder
Ministerio de Ciencia e Innovación (España)
2024-07-02T11:55:36Z
2024-07-02T11:55:36Z
2024-05
Blanco-Martín T, Alonso-García I, González-Pinto L, Outeda-García M, Guijarro-Sánchez P, López-Hernández I, Pérez-Vázquez M, Aracil B, López-Cerero L, Fraile-Ribot P, Oliver A, Vázquez-Ucha JC, Beceiro A, Bou G, Arca-Suárez J; GEMARA/SEIMC-CIBERINFEC Study Group on the activity and resistance mechanisms to new β-lactams and β-lactamase inhibitors (PROTECT). 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. Int J Antimicrob Agents. 2024 May;63(5):107150.
10.1016/j.ijantimicag.2024.107150
1872-7913
International journal of antimicrobial agents
38513748
http://hdl.handle.net/20.500.12105/19906
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.
eng
β-lactamases
Cefiderocol
β-lactam/β-lactamase inhibitor
Combinations
Permeability
Double-carbapenemase
Escherichia coli
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
research article
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