Does the activity of the combination of imipenem and colistin in vitro exceed the problem of resistance in metallo-beta-lactamase-producing Klebsiella pneumoniae isolates?

Antimicrob Agents Chemother. 2009 May;53(5):2133-5. doi: 10.1128/AAC.01271-08. Epub 2009 Mar 2.

Abstract

Using time-kill methodology, we investigated the interactions of an imipenem-colistin combination against 42 genetically distinct Klebsiella pneumoniae clinical isolates carrying a bla(VIM-1)-type gene. Irrespective of the imipenem MIC, the combination was synergistic (50%) or indifferent (50%) against colistin-susceptible strains, while it was antagonistic (55.6%) and rarely synergistic (11%) against non-colistin-susceptible strains (with synergy being observed only against strains with colistin MICs of 3 to 4 microg/ml). The combination showed improved bactericidal activity against isolates susceptible either to both agents or to colistin.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Colistin / pharmacology*
  • Drug Interactions
  • Drug Resistance, Bacterial*
  • Drug Therapy, Combination
  • Humans
  • Imipenem / pharmacology*
  • Klebsiella pneumoniae / classification
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / enzymology
  • Klebsiella pneumoniae / genetics
  • Microbial Sensitivity Tests
  • beta-Lactamases / biosynthesis
  • beta-Lactamases / genetics

Substances

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