Identification of Novel VEB β-Lactamase Enzymes and Their Impact on Avibactam Inhibition

Antimicrob Agents Chemother. 2016 Apr 22;60(5):3183-6. doi: 10.1128/AAC.00047-16. Print 2016 May.

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.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Azabicyclo Compounds / pharmacology*
  • Bacterial Proteins / metabolism
  • Ceftazidime / pharmacology
  • Drug Combinations
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / enzymology*
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / enzymology*
  • beta-Lactamase Inhibitors / pharmacology*
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Bacterial Proteins
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • beta-Lactamase Inhibitors
  • avibactam
  • Ceftazidime
  • beta-Lactamases