Impaired Inhibition by Avibactam and Resistance to the Ceftazidime-Avibactam Combination Due to the D 179 Y Substitution in the KPC-2 β-Lactamase | Zendy

Fabrice Compain | Zendy; Michel Arthur | Zendy

Open Access

Impaired Inhibition by Avibactam and Resistance to the Ceftazidime-Avibactam Combination Due to the D ¹⁷⁹ Y Substitution in the KPC-2 β-Lactamase

Author(s) -

Fabrice Compain,

Michel Arthur

Publication year - 2017

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.00451-17

Subject(s) - aztreonam , ceftazidime/avibactam , avibactam , beta lactamase inhibitors , klebsiella pneumoniae , ceftazidime , imipenem , drug resistance , medicine , microbiology and biotechnology , antibiotics , chemistry , pharmacology , antibiotic resistance , biology , bacteria , biochemistry , escherichia coli , genetics , pseudomonas aeruginosa , gene

The ceftazidime-avibactam antibiotic combination was recently shown to be at risk for the emergence of resistance under treatment. To gain insight into the underlying mechanism, we have analyzed the catalytic properties of aKlebsiella pneumoniae carbapenemase type 2 (KPC-2) β-lactamase harboring the D179 Y substitution. We show that impaired inhibition by avibactam combined with significant residual activity for ceftazidime hydrolysis accounts for the resistance. In contrast, the D179 Y substitution abolished the hydrolysis of aztreonam and imipenem, indicating that these drugs might provide therapeutic alternatives.

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