The therapeutic effect of tigecycline, unlike that of Ceftazidime, is not influenced by whether the Klebsiella pneumoniae strain produces extended-spectrum β-lactamases in experimental pneumonia in rats

Antimicrob Agents Chemother. 2013 Jan;57(1):643-6. doi: 10.1128/AAC.01154-12. Epub 2012 Nov 5.

Abstract

The efficacies of tigecycline and ceftazidime against fatal pneumonia in rats caused by an extended-spectrum β-lactamase (ESBL)-positive Klebsiella pneumoniae strain or its wild-type (WT) progenitor were compared. Ceftazidime at 12.5 or 50 mg/kg of body weight twice daily (b.i.d.) was effective (50% or 100% rat survival) in pneumonia caused by the WT isolate but unsuccessful (100% rat mortality) in pneumonia caused by the ESBL-positive variant. In contrast, tigecycline at 6.25, 12.5, or 25 mg/kg b.i.d. showed dosage-dependent efficacy up to 100% rat survival irrespective of the ESBL character of the infecting organism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology*
  • Area Under Curve
  • Ceftazidime / pharmacology
  • Dose-Response Relationship, Drug
  • Klebsiella Infections / blood
  • Klebsiella Infections / drug therapy*
  • Klebsiella Infections / microbiology
  • Klebsiella Infections / mortality
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / growth & development
  • Lung / drug effects*
  • Lung / microbiology
  • Male
  • Microbial Sensitivity Tests
  • Minocycline / analogs & derivatives*
  • Minocycline / blood
  • Minocycline / pharmacokinetics
  • Minocycline / pharmacology
  • Pneumonia, Bacterial / blood
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / microbiology
  • Pneumonia, Bacterial / mortality
  • Rats
  • Survival Analysis
  • Tigecycline
  • beta-Lactamases / biosynthesis*

Substances

  • Anti-Bacterial Agents
  • Tigecycline
  • Ceftazidime
  • beta-Lactamases
  • Minocycline