Spotlight on ceftazidime/avibactam: A New Option for MDR Gram-negative Infections

J Antimicrob Chemother. 2016 Oct;71(10):2713-22. doi: 10.1093/jac/dkw239. Epub 2016 Jul 17.

Abstract

During the last decade infections caused by MDR Gram-negative bacteria (GNB) have become increasingly prevalent. Because of their high morbidity and mortality rates, these infections constitute a serious threat to public health worldwide. Ceftazidime/avibactam is a new approved agent combining ceftazidime and a novel β-lactamase inhibitor with activity against various β-lactamases produced by MDR GNB. Avibactam has a spectrum of inhibition of class A and C β-lactamases, including ESBLs, AmpC and Klebsiella pneumoniae carbapenemase (KPC) enzymes. Thus, combination with this inhibitor expands ceftazidime's spectrum of activity to MDR Enterobacteriaceae and Pseudomonas aeruginosa strains. In Phase II clinical trials of patients with complicated intra-abdominal infections and complicated urinary tract infections ceftazidime/avibactam exhibited clinical efficacy comparable to those of meropenem and imipenem/cilastatin, respectively. A Phase III clinical trial confirmed the efficacy of ceftazidime/avibactam in patients with MDR Enterobacteriaceae and P. aeruginosa infections. Microbiological surveillance studies, in vivo animal models of infection and pharmacokinetic/pharmacodynamic target attainment analyses are also discussed, to assess the potential role of this new drug in the treatment of infections caused by MDR GNB.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / therapeutic use*
  • Bacterial Proteins / antagonists & inhibitors
  • Ceftazidime / administration & dosage
  • Ceftazidime / therapeutic use*
  • Clinical Trials as Topic
  • Drug Resistance, Multiple, Bacterial*
  • Drug Therapy, Combination
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Intraabdominal Infections / drug therapy
  • Klebsiella pneumoniae / drug effects
  • Mice
  • Microbial Sensitivity Tests
  • Urinary Tract Infections / drug therapy
  • beta-Lactamase Inhibitors / therapeutic use
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Bacterial Proteins
  • beta-Lactamase Inhibitors
  • avibactam
  • Ceftazidime
  • beta-Lactamases
  • carbapenemase