title: Emergence of pan-resistance in KPC-2 carbapenemase-producing Klebsiella pneumoniae in Crete, Greece: a close call.
abstract: OBJECTIVE
  KPC-2-producing Klebsiella pneumoniae (KPC-KP) ST258 has been rapidly expanding and is often associated with serious nosocomial infections. Last-line antibiotics such as colistin and tigecycline often remain the only treatment option. We describe here the evolving genetic background of KPC-KP isolates in Crete, Greece.
  
  
  METHODS
  We tested the antibiotic susceptibility of 34 clinical isolates from patients hospitalized in 2010 and 2013-14. Whole-genome sequences of these isolates were analysed for acquired resistance genes and gene mutations.
  
  
  RESULTS
  All KPC-KP isolates belonged to ST258 with the exception of one ST147 isolate. From 2014, 26% of isolates were non-susceptible to all antibiotics, compared with 0 of 11 isolates from 2010. Colistin resistance was associated with mutations in mgrB, which was present in 61% of isolates from 2014. Core-genome MLST analysis showed that pan-resistant isolates were closely related and appeared in two separate clusters.
  
  
  CONCLUSIONS
  KPC-KP is rapidly evolving to pan-resistance in Crete. We identified molecular resistance markers for pan-resistant isolates and showed that core-genome MLST is a promising tool for molecular fingerprinting of KPC-KP ST258.
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Bathoorn
authors.affiliation: Department of Internal Medicine, Infectious Diseases Unit, University Hospital of Heraklion, Crete, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Tsioutis
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: da Silva Voorham
authors.affiliation: Laboratory of Clinical Bacteriology and Molecular Microbiology, Faculty of Medicine, University of Crete, Heraklion, Greece.
authors.forename: E V
authors.initials: EV
authors.lastname: Scoulica
authors.affiliation: Department of Internal Medicine, Rethymnon General Hospital, Rethymnon, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Ioannidou
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Rossen
authors.affiliation: Department of Internal Medicine, Infectious Diseases Unit, University Hospital of Heraklion, Crete, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Gikas
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands alex.friedrich@umcg.nl.
authors.forename: A W
authors.initials: AW
authors.lastname: Friedrich
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Grundmann
mesh_terms: D024901:Drug Resistance, Multiple, Bacterial; D016680:Genome, Bacterial; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D001618:beta-Lactamases; C547585:beta-lactamase KPC-2, Klebsiella pneumoniae