title: Identification of Novel VEB β-Lactamase Enzymes and Their Impact on Avibactam Inhibition.
abstract: Ceftazidime-avibactam has activity against Pseudomonas aeruginosa and Enterobacteriaceae expressing numerous class A and class C β-lactamases, although the ability to inhibit many minor enzyme variants has not been established. Novel VEB class A β-lactamases were identified during characterization of surveillance isolates. The cloned novel VEB β-lactamases possessed an extended-spectrum β-lactamase phenotype and were inhibited by avibactam in a concentration-dependent manner. The residues that comprised the avibactam binding pocket were either identical or functionally conserved. These data demonstrate that avibactam can inhibit VEB β-lactamases.
authors.affiliation: Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA slahiri@macrolidepharma.com.
authors.forename: Sushmita D
authors.initials: SD
authors.lastname: Lahiri
authors.affiliation: Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Alm
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D002442:Ceftazidime / Q000494:pharmacology; D004338:Drug Combinations; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology*; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D001426:Bacterial Proteins; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D065093:beta-Lactamase Inhibitors; C543519:avibactam; D002442:Ceftazidime; D001618:beta-Lactamases