title: Outbreak of KPC-3 Producing Carbapenem-Resistant Klebsiella pneumoniae in a US Pediatric Hospital.
abstract: BACKGROUND
  The increase in carbapenem-resistant Enterobacteriaceae (CRE) infections is a critical public health issue. We recently experienced the largest single-center pediatric outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) at our hospital. The objective of this study was to describe the molecular epidemiology of this outbreak before and after infection-prevention interventions.
  
  
  METHODS
  All positive cultures and associated clinical conditions were reviewed to determine whether health care-associated infections (HAIs) exist. HAIs were defined using Centers for Disease Control and Prevention guidelines. CRKP isolates were collected and screened for the presence of β-lactamase genes. Strain relatedness of CRKP isolates was determined by field-inversion gel electrophoresis (FIGE) and multilocus sequence typing (MLST). Polymerase chain reaction (PCR) amplification and sequencing of blaTEM, blaSHV, and blaKPC genes were performed on representative isolates.
  
  
  RESULTS
  During March-July 2010, 18 CRKP isolates were recovered from 15 unique patients. Six isolates were considered HAIs; all were central-line-associated bloodstream infections. All isolates testing positive by PCR for blaKPC were found to carry KPC-3 in transposon Tn4401 isotype "b." FIGE revealed 2 prevalent patterns (accounting for 10 and 3 CRKP isolates, respectively) that MLST demonstrated to consist entirely of strains from ST730; the remaining FIGE types corresponded to ST14, ST15, and ST1559 (a single-locus variant of ST730), with these alternate backgrounds appearing later in the outbreak. New CRKP cases decreased after the implementation of infection-control interventions. All isolates were ciprofloxacin sensitive.
  
  
  CONCLUSIONS
  Molecular analyses document the introduction of a KPC-3-producing CRKP clone into our hospital setting, though some isolates appear to have other mechanisms of carbapenem resistance. The transition to a polyclonal epidemiology suggests that the initial outbreak was due to nosocomial spread of a single ST730 clone, while latter isolates may have been secondary to the introduction of a blaKPC-3/Tn4401 isotype "b"-containing plasmid into other K pneumoniae strain backgrounds versus new carbapenemase-producing bacteria.
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor.
authors.forename: Terri
authors.initials: T
authors.lastname: Stillwell
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center.
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center.
authors.forename: Karen
authors.initials: K
authors.lastname: Barbadora
authors.affiliation: Infection Control Department, University of Pittsburgh Medical Center Mercy.
authors.forename: Juliet G
authors.initials: JG
authors.lastname: Ferrelli
authors.affiliation: Infection Control Department, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pennsylvania.
authors.forename: Terri L
authors.initials: TL
authors.lastname: Roberts
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital, Washington.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Weissman
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center.
authors.forename: Andrew
authors.initials: A
authors.lastname: Nowalk
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015780:Carbapenems / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D003428:Cross Infection / Q000453:epidemiology; D004196:Disease Outbreaks; D024881:Drug Resistance, Bacterial; D005260:Female; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D007710:Klebsiella Infections / Q000188:drug therapy / Q000453:epidemiology*; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects*; D008297:Male; D058885:Multilocus Sequence Typing; D016133:Polymerase Chain Reaction; D014481:United States; D001618:beta-Lactamases
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D001618:beta-Lactamases
keywords: Klebsiella pneumoniae; carbapenemase; infection control; nosocomial infection; pediatric