Outbreak of KPC-3 Producing Carbapenem-Resistant Klebsiella pneumoniae in a US Pediatric Hospital

J Pediatric Infect Dis Soc. 2015 Dec;4(4):330-8. doi: 10.1093/jpids/piu080. Epub 2014 Nov 3.


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.

Keywords: Klebsiella pneumoniae; carbapenemase; infection control; nosocomial infection; pediatric.

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / pharmacology
  • Carbapenems / pharmacology*
  • Child
  • Child, Preschool
  • Cross Infection / epidemiology
  • Disease Outbreaks*
  • Drug Resistance, Bacterial*
  • Female
  • Hospitals, Pediatric
  • Humans
  • Infant
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / epidemiology*
  • Klebsiella pneumoniae / classification
  • Klebsiella pneumoniae / drug effects*
  • Male
  • Multilocus Sequence Typing
  • Polymerase Chain Reaction
  • United States
  • beta-Lactamases


  • Anti-Bacterial Agents
  • Carbapenems
  • beta-Lactamases