title: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae at a single institution: insights into endemicity from whole-genome sequencing.
abstract: The global emergence of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) multilocus sequence type ST258 is widely recognized. Less is known about the molecular and epidemiological details of non-ST258 K. pneumoniae in the setting of an outbreak mediated by an endemic plasmid. We describe the interplay of blaKPC plasmids and K. pneumoniae strains and their relationship to the location of acquisition in a U.S. health care institution. Whole-genome sequencing (WGS) analysis was applied to KPC-Kp clinical isolates collected from a single institution over 5 years following the introduction of blaKPC in August 2007, as well as two plasmid transformants. KPC-Kp from 37 patients yielded 16 distinct sequence types (STs). Two novel conjugative blaKPC plasmids (pKPC_UVA01 and pKPC_UVA02), carried by the hospital index case, accounted for the presence of blaKPC in 21/37 (57%) subsequent cases. Thirteen (35%) isolates represented an emergent lineage, ST941, which contained pKPC_UVA01 in 5/13 (38%) and pKPC_UVA02 in 6/13 (46%) cases. Seven (19%) isolates were the epidemic KPC-Kp strain, ST258, mostly imported from elsewhere and not carrying pKPC_UVA01 or pKPC_UVA02. Using WGS-based analysis of clinical isolates and plasmid transformants, we demonstrate the unexpected dispersal of blaKPC to many non-ST258 lineages in a hospital through spread of at least two novel blaKPC plasmids. In contrast, ST258 KPC-Kp was imported into the institution on numerous occasions, with other blaKPC plasmid vectors and without sustained transmission. Instead, a newly recognized KPC-Kp strain, ST941, became associated with both novel blaKPC plasmids and spread locally, making it a future candidate for clinical persistence and dissemination.
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA Clinical Microbiology, Department of Pathology, University of Virginia Health System, Charlottesville, Virginia, USA ajm5b@virginia.edu.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Mathers
authors.affiliation: Modernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
authors.forename: Nicole
authors.initials: N
authors.lastname: Stoesser
authors.affiliation: Modernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Sheppard
authors.affiliation: Modernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Pankhurst
authors.affiliation: Modernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
authors.forename: Adam
authors.initials: A
authors.lastname: Giess
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Yeh
authors.affiliation: Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Xavier
authors.initials: X
authors.lastname: Didelot
authors.affiliation: Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Turner
authors.affiliation: Icahn Institute and Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, New York, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Sebra
authors.affiliation: Icahn Institute and Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, New York, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kasarskis
authors.affiliation: Modernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom.
authors.forename: Tim
authors.initials: T
authors.lastname: Peto
authors.affiliation: Modernizing Medical Microbiology Consortium, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom Public Health England, Microbiology Services, London, United Kingdom.
authors.forename: Derrick
authors.initials: D
authors.lastname: Crook
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA Office of Hospital Epidemiology, University of Virginia Health System, Charlottesville, Virginia, USA.
authors.forename: Costi D
authors.initials: CD
authors.lastname: Sifri
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D003428:Cross Infection / Q000453:epidemiology*; D004196:Disease Outbreaks; D006761:Hospitals; D006801:Humans; D007710:Klebsiella Infections / Q000453:epidemiology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000235:genetics*; D017720:Molecular Epidemiology; D010957:Plasmids / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase