Activity of imipenem against VIM-1 metallo-beta-lactamase-producing Klebsiella pneumoniae in the murine thigh infection model

Clin Microbiol Infect. 2007 Feb;13(2):202-205. doi: 10.1111/j.1469-0691.2006.01590.x.


The in-vivo activity of imipenem against VIM-1-producing Klebsiella pneumoniae (VPKP) was assessed in a thigh infection model in neutropenic mice. Animals were infected with three VPKP isolates (imipenem MICs 2, 4 and 32 mg/L, respectively) and a susceptible clinical isolate (MIC 0.125 mg/L) that did not produce any beta-lactamase with broad-spectrum activity. Bacterial density at the site of infection was determined after imipenem treatment (30 and 60 mg/kg every 2 h for 24 h). The log(10) reduction in CFU/thigh was greatest for the wild-type isolate, intermediate for the two imipenem-susceptible VPKP isolates, and lowest for the imipenem-resistant VPKP isolate. Whilst in-vivo imipenem activity appeared reduced against in-vitro susceptible VIM-1 producers compared with a VIM-1-negative control, an increased drug dosage could moderate this reduction.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Imipenem / blood
  • Imipenem / pharmacology*
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / enzymology*
  • Klebsiella pneumoniae / isolation & purification
  • Mice
  • Mice, Inbred ICR
  • Microbial Sensitivity Tests
  • Muscular Diseases / drug therapy*
  • Muscular Diseases / microbiology
  • Neutropenia / blood
  • Time Factors
  • beta-Lactamases / biosynthesis


  • Anti-Bacterial Agents
  • Imipenem
  • VIM-1 metallo-beta-lactamase
  • beta-Lactamases