Clonal Spread of KPC-2 Carbapenemase-Producing Klebsiella Pneumoniae Strains in Greece

J Antimicrob Chemother. 2009 Aug;64(2):348-52. doi: 10.1093/jac/dkp207. Epub 2009 Jun 13.


Objectives: KPC-possessing Klebsiella pneumoniae have been found to be widespread in several regions but are still rarely detected in Europe. We describe the characteristics of an outbreak caused by KPC producers in a tertiary care Greek hospital.

Methods: During a 12 month period (October 2007-September 2008), 47 patients in Hippokration University Hospital yielded K. pneumoniae isolates that exhibited reduced susceptibility to carbapenems and were phenotypically positive for carbapenemase production but negative for metallo-beta-lactamase (MBL) production. Single patient isolates were tested by Vitek 2, Etest, agar dilution MICs, phenotypic assays and PFGE. Carbapenemase and other beta-lactamase genes were identified by PCR and sequencing. Patient records were retrospectively reviewed to access co-morbidities, antibiotic exposure prior to infection and outcome.

Results: The 47 K. pneumoniae isolates exhibited various susceptibilities to imipenem and meropenem; all were non-susceptible to ertapenem and several other antibiotics but most were susceptible to gentamicin, colistin and tigecycline. PFGE classified the isolates into two clonal types, with the predominant type, which was closely related to that of hyperepidemic strains from the USA and Israel, comprising three subtypes. All isolates carried the bla(KPC-2) gene; 45 also carried bla(SHV-12) and 29 bla(TEM-1). Patients were hospitalized in nine different units. The median length of hospital stay prior to KPC isolation was 21 days; 38 patients (80.9%) had evidence of clinical infection due to a KPC producer and 16 (34%) had bacteraemia. The crude mortality rate was 27.7%. A beta-lactam/beta-lactamase inhibitor combination was the most frequently administered antimicrobial prior to KPC isolation (20 patients; 42.5%), whereas only nine patients (19.1%) had prior carbapenem use.

Conclusions: This study presents for the first time a wide intrahospital spread of KPC-producing K. pneumoniae clones in a European hospital. The KPC producers were rapidly disseminated in several units, indicating the difficulty in restraining such multidrug-resistant clones when they have been established in a hospital environment.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Typing Techniques
  • Cluster Analysis
  • DNA Fingerprinting
  • DNA, Bacterial / genetics
  • Disease Outbreaks*
  • Drug Resistance, Multiple, Bacterial*
  • Electrophoresis, Gel, Pulsed-Field
  • Female
  • Genotype
  • Greece / epidemiology
  • Humans
  • Klebsiella Infections / epidemiology*
  • Klebsiella Infections / microbiology*
  • Klebsiella pneumoniae / classification
  • Klebsiella pneumoniae / enzymology*
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / isolation & purification
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Polymerase Chain Reaction / methods
  • Sequence Analysis, DNA
  • beta-Lactamases / biosynthesis*
  • beta-Lactamases / genetics


  • Anti-Bacterial Agents
  • DNA, Bacterial
  • beta-lactamase KPC-2
  • beta-Lactamases