title: Evolution and Transmission of Carbapenem-Resistant Klebsiella pneumoniae Expressing the blaOXA-232 Gene During an Institutional Outbreak Associated With Endoscopic Retrograde Cholangiopancreatography.
abstract: BACKGROUND
  Whole-genome sequencing (WGS) is an emerging and powerful technique by which to perform epidemiological studies in outbreak situations.
  
  
  METHODS
  WGS was used to identify and evaluate an outbreak of OXA-232-expressing carbapenem-resistant Klebsiella pneumoniae (CRKP) transmitted to 16 patients over the course of 40 weeks via endoscopic retrograde cholangiopancreatography procedures at a single institution. WGS was performed on 32 OXA-232 CRKP isolates (1-7 per patient) and single-nucleotide variants (SNVs) were analyzed, with reference to the index patient's isolate.
  
  
  RESULTS
  Interhost genetic diversity of isolates was between 0 and 15 SNVs during the outbreak; molecular clock calculations estimated 12.31 substitutions per genome per year (95% credibility interval, 7.81-17.05). Both intra- and interpatient diversification at the plasmid and transposon level was observed, significantly impacting the antibiogram of outbreak isolates. The majority of isolates evaluated (n = 27) harbored a blaCTX-M-15 gene, but some (n = 5) lacked the transposon carrying this gene, which resulted in susceptibility to aztreonam and third- and fourth-generation cephalosporins. Similarly, an isolate from a colonized patient lacked the transposon carrying rmtF and aac(6')lb genes, resulting in susceptibility to aminoglycosides.
  
  
  CONCLUSIONS
  This study broadens the understanding of how bacteria diversify at the genomic level over the course of a defined outbreak and provides reference for future outbreak investigations.
authors.affiliation: Pathology and LaboratoryMedicine, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Shangxin
authors.initials: S
authors.lastname: Yang
authors.affiliation: Pathology and LaboratoryMedicine, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Peera
authors.initials: P
authors.lastname: Hemarajata
authors.affiliation: Pathology and LaboratoryMedicine, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Janet
authors.initials: J
authors.lastname: Hindler
authors.affiliation: Mi Next Generation Science Core Laboratory, Children's Hospital Los Angeles, California.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: Mi Next Generation Science Core Laboratory, Children's Hospital Los Angeles, California.
authors.forename: Helty
authors.initials: H
authors.lastname: Adisetiyo
authors.affiliation: Mi Next Generation Science Core Laboratory, Children's Hospital Los Angeles, California.
authors.forename: Grace
authors.initials: G
authors.lastname: Aldrovandi
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Robert
authors.initials: R
authors.lastname: Sebra
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kasarskis
authors.affiliation: National Center for Emerging and Zoonotic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Duncan
authors.initials: D
authors.lastname: MacCannell
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom; and.
authors.forename: Xavier
authors.initials: X
authors.lastname: Didelot
authors.affiliation: Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Dana
authors.initials: D
authors.lastname: Russell
authors.affiliation: Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Rubin
authors.affiliation: Pathology and LaboratoryMedicine, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Romney
authors.initials: R
authors.lastname: Humphries
mesh_terms: D015780:Carbapenems / Q000494:pharmacology*; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000009:adverse effects*; D003428:Cross Infection; D004196:Disease Outbreaks; D004789:Enzyme Activation; D014644:Genetic Variation; D016680:Genome, Bacterial; D006801:Humans; D007710:Klebsiella Infections / Q000453:epidemiology* / Q000635:transmission*; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics; D000073336:Whole Genome Sequencing; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D015780:Carbapenems; D001618:beta-Lactamases
keywords: CRE outbreak; ERCP; OXA-232; carbapenem-resistant Klebsiella pneumoniae.; whole-genome sequencing