Characteristics of meropenem heteroresistance in Klebsiella pneumoniae carbapenemase (KPC)-producing clinical isolates of K. pneumoniae

J Clin Microbiol. 2010 Jul;48(7):2601-4. doi: 10.1128/JCM.02134-09. Epub 2010 May 26.


Meropenem heteroresistance was investigated in six apparently meropenem-susceptible, Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) clinical isolates, compared with that in carbapenemase-negative, meropenem-susceptible controls. In population analyses, the KPC-KP isolates grew at meropenem concentrations of 64 to 256 microg/ml. Heteroresistant colonies had significantly elevated expression of the bla(KPC) gene compared with the native populations but did not retain heteroresistance when subcultured in drug-free media. Time-kill assays indicated that meropenem alone was not bactericidal against KPC-KP but efficiently killed the control strains.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Drug Resistance, Bacterial / genetics*
  • Humans
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / genetics
  • Meropenem
  • Microbial Sensitivity Tests
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thienamycins / pharmacology*
  • beta-Lactamases / genetics*


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Thienamycins
  • beta-Lactamases
  • Meropenem