Reduced imipenem susceptibility in Klebsiella pneumoniae clinical isolates with plasmid-mediated CMY-2 and DHA-1 beta-lactamases co-mediated by porin loss

Kyungwon Lee, Dongeun Yong, Yeong Seon Choi, Jong Hwa Yum, June Myung Kim, Neil Woodford, David M Livermore, Yunsop Chong

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We investigated the resistance mechanisms and clonality among 42 imipenem-non-susceptible Klebsiella pneumoniae isolated at a tertiary care hospital in Korea. Two isolates had bla(VIM-2) alleles, whereas bla(CMY-2)- and bla(DHA-1)-like alleles were detected in 24 and 16 isolates, respectively, with these enzymes confirmed by sequencing for representative isolates. Transfer of bla(CMY-2) and bla(DHA-1) was achieved by conjugation. Addition of 300 mg/L 3-aminophenylboronic acid (APB) reduced the minimum inhibitory concentration for 90% of the organisms (MIC(90)) of imipenem and meropenem eight- and four-fold, respectively, for the bla(CMY-2)- and bla(DHA-1)-positive isolates, confirming the role of these enzymes in resistance. SDS-PAGE of outer membrane proteins for representative isolates showed lack or greatly diminished expression of OmpK35 and OmpK36 porins. Pulsed-field gel electrophoresis of XbaI-restricted genomic DNA revealed two closely related clusters among 23 bla(CMY-2)-positive isolates, whereas those with bla(DHA-1) were more heterogeneous. In conclusion, reduced imipenem susceptibility among K. pneumoniae at this Korean hospital was largely co-mediated by production of plasmid-mediated AmpC beta-lactamases along with lack or greatly diminished expression of OmpK35 and OmpK36 porins.
Original languageEnglish
Pages (from-to)201-206
Number of pages6
JournalInternational Journal of Antimicrobial Agents
Issue number2
Publication statusPublished - Feb 2007


  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Electrophoresis, Gel, Pulsed-Field
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Imipenem
  • Isoelectric Focusing
  • Klebsiella pneumoniae
  • Microbial Sensitivity Tests
  • Plasmids
  • Porins
  • beta-Lactamases

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