In vivo selection of imipenem-resistant Klebsiella pneumoniae producing extended-spectrum beta-lactamase CTX-M-15 and plasmid-encoded DHA-1 cephalosporinase

Int J Antimicrob Agents. 2010 Mar;35(3):265-8. doi: 10.1016/j.ijantimicag.2009.10.021.

Abstract

Four Klebsiella pneumoniae isolates (KP1-4) were recovered sequentially from an infected patient. Whilst KP1-3 were resistant to all beta-lactams except carbapenems, KP4 recovered after 24 days of imipenem-containing treatment showed additional resistance to carbapenems. No carbapenem hydrolysis could be identified in KP4. Molecular characterisation revealed that KP1-4 were indistinguishable by pulsed-field gel electrophoresis, contained a 95-kb self-transferable plasmid harbouring bla(CTXM-15) and bla(TEM-1) genes and a 65-kb plasmid that was not transferred by conjugation into Escherichia coli, and harboured the plasmid-mediated bla(DHA-1) AmpC beta-lactamase gene. In addition, KP4 failed to express OmpK36 owing to a point mutation leading to a premature stop of the protein. This study demonstrates development of carbapenem resistance related to loss of OmpK36 expression in a K. pneumoniae isolate harbouring extended-spectrum beta-lactamase and plasmid-mediated cephalosporinase genes following prolonged imipenem exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Typing Techniques
  • DNA Fingerprinting
  • DNA, Bacterial / genetics
  • Drug Resistance, Bacterial*
  • Electrophoresis, Gel, Pulsed-Field
  • Humans
  • Imipenem / pharmacology*
  • Imipenem / therapeutic use
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / microbiology*
  • Klebsiella pneumoniae / classification
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / enzymology
  • Klebsiella pneumoniae / isolation & purification
  • Microbial Sensitivity Tests
  • Plasmids
  • Selection, Genetic*
  • beta-Lactamases / biosynthesis*

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Imipenem
  • beta-Lactamases