Activities of ceftazidime, ceftaroline, and aztreonam alone and combined with avibactam against isogenic Escherichia coli strains expressing selected single β-lactamases

Diagn Microbiol Infect Dis. 2015 May;82(1):65-9. doi: 10.1016/j.diagmicrobio.2015.02.003. Epub 2015 Feb 14.

Abstract

Avibactam is a novel β-lactamase inhibitor that restores the activity of otherwise hydrolyzed β-lactams against Gram-negative bacteria expressing different classes of serine β-lactamases. In the last decade, β-lactam-avibactam combinations were tested against a variety of clinical isolates expressing multiple commonly encountered β-lactamases. Here, we analyzed isogenic Escherichia coli strains expressing selected single β-lactamase genes that were not previously tested or were not characterized in an isogenic background. The activities of ceftazidime, ceftaroline, and aztreonam alone and in combination with 4 mg/L of avibactam, as well as comparator agents, were assessed against a unique collection of isogenic strains of E. coli carrying selected extended-spectrum, inhibitor-resistant, and/or carbapenem-hydrolyzing bla genes. When combined with avibactam, ceftazidime, ceftaroline, or aztreonam MICs were reduced for 91.4%, 80.0%, and 80.0% of isolates, respectively. The data presented add to our understanding of the microbiologic spectrum of these β-lactams with avibactam and serve as a reference for further studies.

Keywords: Avibactam; Carbapenemase; ESBL; Inhibitor-resistance; β-Lactamase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azabicyclo Compounds / pharmacology*
  • Aztreonam / pharmacology
  • Ceftaroline
  • Ceftazidime / pharmacology
  • Cephalosporins / pharmacology
  • Escherichia coli / drug effects*
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Humans
  • Microbial Sensitivity Tests
  • beta-Lactamase Inhibitors / pharmacology*
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism*
  • beta-Lactams / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Cephalosporins
  • beta-Lactamase Inhibitors
  • beta-Lactams
  • avibactam
  • Ceftazidime
  • beta-Lactamases
  • Aztreonam