title: Genomic Epidemiology of an Endoscope-Associated Outbreak of Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae.
abstract: Increased incidence of infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) was noted among patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) at a single hospital. An epidemiologic investigation identified KPC-Kp and non-KPC-producing, extended-spectrum β-lactamase (ESBL)-producing Kp in cultures from 2 endoscopes. Genotyping was performed on patient and endoscope isolates to characterize the microbial genomics of the outbreak. Genetic similarity of 51 Kp isolates from 37 patients and 3 endoscopes was assessed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Five patient and 2 endoscope isolates underwent whole genome sequencing (WGS). Two KPC-encoding plasmids were characterized by single molecule, real-time sequencing. Plasmid diversity was assessed by endonuclease digestion. Genomic and epidemiologic data were used in conjunction to investigate the outbreak source. Two clusters of Kp patient isolates were genetically related to endoscope isolates by PFGE. A subset of patient isolates were collected post-ERCP, suggesting ERCP endoscopes as a possible source. A phylogeny of 7 Kp genomes from patient and endoscope isolates supported ERCP as a potential source of transmission. Differences in gene content defined 5 ST258 subclades and identified 2 of the subclades as outbreak-associated. A novel KPC-encoding plasmid, pKp28 helped define and track one endoscope-associated ST258 subclade. WGS demonstrated high genetic relatedness of patient and ERCP endoscope isolates suggesting ERCP-associated transmission of ST258 KPC-Kp. Gene and plasmid content discriminated the outbreak from endemic ST258 populations and assisted with the molecular epidemiologic investigation of an extended KPC-Kp outbreak.
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jane W
authors.initials: JW
authors.lastname: Marsh
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America.|Public Health Dynamics Laboratory, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Mary G
authors.initials: MG
authors.lastname: Krauland
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jemma S
authors.initials: JS
authors.lastname: Nelson
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Schlackman
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Brooks
authors.affiliation: Division of Microbiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
authors.forename: A William
authors.initials: AW
authors.lastname: Pasculle
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Shutt
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Doi
authors.affiliation: Division of Hospital Epidemiology and Infection Control, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Querry
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America.|Division of Hospital Epidemiology and Infection Control, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Carlene A
authors.initials: CA
authors.lastname: Muto
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Lee H
authors.initials: LH
authors.lastname: Harrison
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000009:adverse effects*; D004196:Disease Outbreaks; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D007710:Klebsiella Infections / Q000201:enzymology / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D007711:Klebsiella pneumoniae / Q000235:genetics / Q000302:isolation & purification; D008297:Male; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase