Klebsiella pneumoniae: development of a mixed population of carbapenem and tigecycline resistance during antimicrobial therapy in a kidney transplant patient

Clin Microbiol Infect. 2012 Jan;18(1):61-6. doi: 10.1111/j.1469-0691.2011.03482.x. Epub 2011 Jul 1.


Nine isolates of Klebsiella pneumoniae were isolated from a renal transplant patient suffering from recurrent urosepsis over a period of 4 months. Imipenem resistance was detected after imipenem-ertapenem therapy. When treatment was switched to tigecycline the K. pneumoniae developed resistance to tigecycline (MIC = 8 mg/L). The nine isolates were tested by determination of agar dilution MICs, phenotypic carbapenemase, extended-spectrum beta-lactamases and metallo-beta-lactamase (MBL) testing and pulsed-field gel electrophoresis. Polymerase chain reaction and sequencing analysis were employed for identification of bla genes and mapping of the integron carrying the MBL gene. The nine isolates were clonally related and all produced the SHV-12 enzyme. Five MBL-producing isolates showed imipenem MICs ranging from 2 to 64 mg/L and all were detected by testing with imipenem and EDTA. The five isolates harboured the bla(VIM-1) gene. Three isolates showed increased tigecycline MICs (4-8 mg/L). Serial blood cultures obtained on the same day resulted in a VIM-positive/tigecycline-susceptible and a VIM-negative/tigecycline-resistant K. pneumoniae isolate. No isolate developed concurrent imipenem and tigecycline resistance. The patient had a persistent urinary tract infection and recurrent bacteraemia caused by a mixed population of Klebesiella pneumoniae isolates adapting to the selective pressure of antimicrobial therapy at the time. The present study is a worrisome example of what could happen when an immunocompromised host is subjected to the pressures of antimicrobial therapy. In addition, we report the first treatment-emergent MIC increase of tigecycline from 0.5 to 8 mg/L in K. pneumoniae.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Base Sequence
  • Carbapenems / pharmacology*
  • Chromosome Mapping
  • Cross Infection
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Humans
  • Kidney Transplantation*
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / isolation & purification
  • Male
  • Microbial Sensitivity Tests
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Sequence Analysis, DNA
  • Tigecycline
  • Urinary Tract Infections / drug therapy
  • Urinary Tract Infections / microbiology
  • beta-Lactamases / genetics


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • Tigecycline
  • beta-Lactamases
  • carbapenemase
  • Minocycline