title: An outbreak of infection due to beta-Lactamase Klebsiella pneumoniae Carbapenemase 2-producing K. pneumoniae in a Greek University Hospital: molecular characterization, epidemiology, and outcomes.
abstract: BACKGROUND
  We describe the emergence and spread of Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing K. pneumoniae at a Greek University hospital.
  
  
  METHODS
  Isolates with a carbapenem minimum inhibitory concentration >1 microg/mL and a negative EDTA-imipenem disk synergy test result were submitted to boronic acid disk test and to polymerase chain reaction (PCR) for KPC gene and sequencing. Records from patients who had KPC-2-producing K. pneumoniae isolated were retrospectively reviewed. Clinical isolates were submitted to molecular typing using pulsed-field gel electrophoresis, and the beta-lactamase content was studied using isoelectric focusing and PCR.
  
  
  RESULTS
  From January 2007 through December 2008, 50 patients (34 in the intensive care unit [ICU]) were colonized (n = 32) or infected (n = 18) by KPC-2-producing K. pneumoniae. Increasing prevalence of KPC-2-producing K. pneumoniae coincided with decreasing prevalence of metallo-beta lactamase-producing isolates in our ICU. Multidrug resistance characterized the studied isolates, with colistin, gentamicin, and fosfomycin being the most active agents. Besides KPC-2, clinical isolates encoded TEM-1-like, SHV-11, SHV-12, CTX-M-15, and LEN-19 enzymes. Four different clonal types were detected; the predominant one comprised 41 single patient isolates (82%). Sporadic multiclonal cases of KPC-2-producing K. pneumoniae infection were identified from September 2007 through May 2008. The outbreak strain was introduced in February 2008 and disseminated rapidly by cross-transmission; 38 patients (76%) were identified after August 2008. Fourteen cases of bacteremia, 2 surgical site infections, 2 lower respiratory tract infections (1 bacteremic), and 1 urinary tract infection were identified. Most patients received a colistin-containing combination treatment. Crude mortality was 58.8% among ICU patients and 37.5% among non-ICU patients, but attributable mortality was 22.2% and 33.3%, respectively.
  
  
  CONCLUSIONS
  The emergence of KPC-2-producing K. pneumoniae in Greek hospitals creates an important challenge for clinicians and hospital epidemiologists, because it is added to the already high burden of antimicrobial resistance.
authors.affiliation: 4th Dept of Internal Medicine, University General Hospital ATTIKON, 1 Rimini Str 124 62, Chaidari, Greece. msouli@med.uoa.gr
authors.forename: Maria
authors.initials: M
authors.lastname: Souli
authors.forename: Irene
authors.initials: I
authors.lastname: Galani
authors.forename: Anastasia
authors.initials: A
authors.lastname: Antoniadou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Papadomichelakis
authors.forename: Garyphallia
authors.initials: G
authors.lastname: Poulakou
authors.forename: Theofano
authors.initials: T
authors.lastname: Panagea
authors.forename: Sofia
authors.initials: S
authors.lastname: Vourli
authors.forename: Loukia
authors.initials: L
authors.lastname: Zerva
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Kanellakopoulou
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D015373:Bacterial Typing Techniques; D016172:DNA Fingerprinting; D004196:Disease Outbreaks; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D006115:Greece / Q000453:epidemiology; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D007710:Klebsiella Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000145:classification / Q000201:enzymology* / Q000302:isolation & purification; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D017720:Molecular Epidemiology; D016896:Treatment Outcome; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001618:beta-Lactamases; C531581:carbapenemase-2, Klebsiella pneumoniae