Details

Autor(en) / Beteiligte

• Blanco-Martín, Tania
• Alonso-García, Isaac
• González-Pinto, Lucía
• Outeda-García, Michelle
• Guijarro-Sánchez, Paula
• López-Hernández, Inmaculada
• Pérez-Vázquez, María
• Aracil, Belén
• López-Cerero, Lorena
• Fraile-Ribot, Pablo
• Oliver, Antonio
• Vázquez-Ucha, Juan Carlos
• Beceiro, Alejandro
• Bou, Germán
• Arca-Suárez, Jorge

Titel

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

Ist Teil von

• International journal of antimicrobial agents, 2024-05, Vol.63 (5), p.107150, Article 107150

Ort / Verlag

Netherlands: Elsevier Ltd

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• •A panel of 82 E. coli recombinant strains producing β-lactamases is developed.•Cefiderocol and new β-lactam/β-lactamase inhibitors are challenged against the panel.•Aztreonam/avibactam and cefepime/zidebactam are the most active options.•Cefepime and meropenem combinations are significantly affected by porin deficiency.•NDM enzymes represent the most challenging resistance determinant. 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. 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. 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. 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. [Display omitted]