Ceftazidime-Avibactam Resistance Mediated by the N <sup>346</sup> Y Substitution in Various AmpC β-Lactamases
Fabrice Compain, Agathe Debray, Pauline Adjadj, Delphine Dorchêne, Michel Arthur
Abstract
Chromosomal and plasmid-borne AmpC cephalosporinases are a major resistance mechanism to β-lactams in Enterobacteriaceae and Pseudomonas aeruginosa . The new β-lactamase inhibitor avibactam effectively inhibits class C enzymes and can fully restore ceftazidime susceptibility. The conserved amino acid residue Asn 346 of AmpC cephalosporinases directly interacts with the avibactam sulfonate. Disruption of this interaction caused by the N 346 Y amino acid substitution in Citrobacter freundii AmpC was previously shown to confer resistance to the ceftazidime-avibactam combination (CAZ-AVI).
Topics & Concepts
Ceftazidime/avibactamChemistryAvibactamCeftazidimeSubstitution (logic)MedicineBiologyBacteriaPseudomonas aeruginosaGeneticsProgramming languageComputer scienceAntibiotic Resistance in BacteriaAntibiotics Pharmacokinetics and EfficacyPharmaceutical and Antibiotic Environmental Impacts