title: Retrospective identification of a previously undetected clinical case of OXA-48-producing K. pneumoniae and E. coli: the importance of adequate detection guidelines.
abstract: BACKGROUND
  The laboratory detection of OXA-48-carbapenemase-producing Enterobacteriaceae is difficult, as minimum inhibition concentrations for carbapenems are often below the clinical breakpoint. In 2011, the Dutch national guideline for the detection of highly resistant micro-organisms was issued, which includes recommendations on the use of carbapenem screening breakpoints for the detection of carbapenemase-producing Enterobacteriaceae.
  
  
  METHODS
  During a validation study of the Check-MDR CT103 microarray (Check-Points, Wageningen, The Netherlands) in 2013, an OXA-48-like carbapenemase gen was identified in two isolates that were previously obtained from a patient with non-Hodgkin lymphoma in 2007. Whole-genome sequencing (WGS) and subsequent BLAST Ringe Image Generator (BRIG) analysis were performed to establish the presence of OXA-48 carbapenemase encoding plasmids and their similarity.
  
  
  RESULTS
  This case report describes the first documented OXA-48-producing Klebsiella pneumonia (ST648) and Escherichia coli (ST866) in the Netherlands. A similar IncL/M plasmid was identified in both strains, suggesting within-patient horizontal transfer.
  
  
  CONCLUSIONS
  This case illustrates that OXA-48-carbapenemase-producing Enterobacteriaceae can be unnoticed without adequate laboratory detection procedures. Our observation stresses the importance of uniform and adequate laboratory methods for the timely and accurate detection of important antimicrobial resistance.
authors.affiliation: Laboratory for Microbiology and Infection Control, Amphia Hospital, PO Box 90158, 4800 RK, Breda, The Netherlands. ina.willemsen@gmail.com.
authors.forename: Ina
authors.initials: I
authors.lastname: Willemsen
authors.affiliation: Department for internal medicine, Amphia Hospital, Breda, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: van Esser
authors.affiliation: Amphia Academy Infectious Disease Foundation, Amphia Hospital, Breda, The Netherlands.|Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Kluytmans-van den Bergh
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: John W
authors.initials: JW
authors.lastname: Rossen
authors.affiliation: Laboratory for Microbiology and Infection Control, Amphia Hospital, PO Box 90158, 4800 RK, Breda, The Netherlands.
authors.forename: Carlo
authors.initials: C
authors.lastname: Verhulst
authors.affiliation: Laboratory for Microbiology and Infection Control, Amphia Hospital, PO Box 90158, 4800 RK, Breda, The Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: Verduin
authors.affiliation: Laboratory for Microbiology and Infection Control, Amphia Hospital, PO Box 90158, 4800 RK, Breda, The Netherlands.|Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Kluytmans
mesh_terms: D001431:Bacteriological Techniques / Q000379:methods* / Q000592:standards; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000032:analysis*; D005260:Female; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D019983:Guideline Adherence; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D008228:Lymphoma, Non-Hodgkin / Q000150:complications; D008403:Mass Screening / Q000379:methods / Q000592:standards; D008875:Middle Aged; D009426:Netherlands; D010957:Plasmids / Q000032:analysis; D017422:Sequence Analysis, DNA; D001618:beta-Lactamases / Q000032:analysis*
chemical_list: D029968:Escherichia coli Proteins; D001618:beta-Lactamases; C000601047:beta-lactamase OXA-48, E coli; C108449:oxacillinase
keywords: Antimicrobial resistance; Detection guidelines; OXA-48; Plasmid transfer; β-lactamase