Unexpected in vivo activity of ceftazidime alone and in combination with avibactam against New Delhi metallo-β-lactamase-producing Enterobacteriaceae in a murine thigh infection model

Antimicrob Agents Chemother. 2014 Nov;58(11):7007-9. doi: 10.1128/AAC.02662-14. Epub 2014 Sep 15.

Abstract

The emergence of the New Delhi metallo-β-lactamase (NDM) among Enterobacteriaceae has become a global concern because of its high levels of in vitro resistance to nearly all available antibiotics. However, recent in vivo studies demonstrated the efficacies of carbapenems against NDM-1-producing isolates despite high MICs. Herein, we report in vivo findings with ceftazidime and ceftazidime-avibactam against an isogenic pair (wild type and NDM-1) and four clinical NDM-producing isolates that demonstrate discordance between MICs measured in vitro and the in vivo activity of ceftazidime-avibactam against this resistant genotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Azabicyclo Compounds / pharmacology*
  • Carbapenems / pharmacology*
  • Ceftazidime / pharmacology*
  • Disease Models, Animal
  • Drug Combinations
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Escherichia coli / isolation & purification
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / microbiology
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / isolation & purification
  • Mice
  • Microbial Sensitivity Tests
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Carbapenems
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • Ceftazidime
  • metallo-beta-lactamase (VIM-13), Pseudomonas aeruginosa
  • beta-Lactamases