title: A Prolonged Outbreak of KPC-3-Producing Enterobacter cloacae and Klebsiella pneumoniae Driven by Multiple Mechanisms of Resistance Transmission at a Large Academic Burn Center.
abstract: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacter cloacae has been recently recognized in the United States. Whole-genome sequencing (WGS) has become a useful tool for analysis of outbreaks and for determining transmission networks of multidrug-resistant organisms in health care settings, including carbapenem-resistant Enterobacteriaceae (CRE). We experienced a prolonged outbreak of CRE E. cloacae and K. pneumoniae over a 3-year period at a large academic burn center despite rigorous infection control measures. To understand the molecular mechanisms that sustained this outbreak, we investigated the CRE outbreak isolates by using WGS. Twenty-two clinical isolates of CRE, including E. cloacae (n = 15) and K. pneumoniae (n = 7), were sequenced and analyzed genetically. WGS revealed that this outbreak, which seemed epidemiologically unlinked, was in fact genetically linked over a prolonged period. Multiple mechanisms were found to account for the ongoing outbreak of KPC-3-producing E. cloacae and K. pneumoniae This outbreak was primarily maintained by a clonal expansion of E. cloacae sequence type 114 (ST114) with distribution of multiple resistance determinants. Plasmid and transposon analyses suggested that the majority of blaKPC-3was transmitted via an identical Tn4401b element on part of a common plasmid. WGS analysis demonstrated complex transmission dynamics within the burn center at levels of the strain and/or plasmid in association with a transposon, highlighting the versatility of KPC-producing Enterobacteriaceae in their ability to utilize multiple modes to resistance gene propagation.
authors.affiliation: Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA kanamori@med.unc.edu.|Hospital Epidemiology, University of North Carolina Health Care, Chapel Hill, North Carolina, USA.
authors.forename: Hajime
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Parobek
authors.affiliation: Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Juliano
authors.affiliation: Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
authors.forename: David
authors.initials: D
authors.lastname: van Duin
authors.affiliation: North Carolina Jaycee Burn Center, University of North Carolina Health Care, Chapel Hill, North Carolina, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Cairns
authors.affiliation: Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.|Hospital Epidemiology, University of North Carolina Health Care, Chapel Hill, North Carolina, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Weber
authors.affiliation: Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.|Hospital Epidemiology, University of North Carolina Health Care, Chapel Hill, North Carolina, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Rutala
mesh_terms: D000328:Adult; D000368:Aged; D001426:Bacterial Proteins / Q000235:genetics; D002053:Burn Units; D004196:Disease Outbreaks; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics*; D016972:Enterobacter cloacae / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D007710:Klebsiella Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009657:North Carolina / Q000453:epidemiology; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D001618:beta-Lactamases; C498060:beta-lactamase KPC-3, Enterobacter cloacae; C495220:beta-lactamase KPC-3, Klebsiella pneumoniae
keywords: Klebsiella pneumoniae carbapenemase (KPC); burn patients; carbapenem-resistant Enterobacteriaceae (CRE); health care-associated infection; outbreak; whole-genome sequencing