Dissemination and characteristics of a novel plasmid-encoded carbapenem-hydrolyzing class D β-lactamase, OXA-436, found in isolates from four patients at six different hospitals in Denmark

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  • Ørjan Samuelsen
  • Frank Hansen
  • Bettina Aasnæs
  • Henrik Hasman
  • Bjarte Aarmo Lund
  • Hanna Kirsti S. Leiros
  • Berit Lilje
  • Jessin Janice
  • Lotte Jakobsen
  • Pia Littauer
  • Lillian M. Søes
  • Holzknecht, Barbara Juliane
  • Andersen, Leif Percival
  • Marc Stegger
  • Paal S. Andersen
  • Anette M. Hammerum

The diversity of OXA-48-like carbapenemases is continually expanding. In this study, we describe the dissemination and characteristics of a novel carbapenem-hydrolyzing class D β-lactamase (CHDL) named OXA-436. In total, six OXA-436-producing Enterobacteriaceae isolates, including Enterobacter asburiae (n = 3), Citrobacter freundii (n = 2), and Klebsiella pneumoniae (n = 1), were identified in four patients in the period between September 2013 and April 2015. All three species of OXA-436-producing Enterobacteriaceae were found in one patient. The amino acid sequence of OXA-436 showed 90.4 to 92.8% identity to the amino acid sequences of other acquired OXA-48-like variants. Expression of OXA-436 in Escherichia coli and kinetic analysis of purified OXA-436 revealed an activity profile similar to that of OXA-48 and OXA-181, with activity against penicillins, including temocillin; limited or no activity against extended-spectrum cephalosporins; and activity against carbapenems. The blaOXA-436 gene was located on a conjugative ∼314-kb IncHI2/IncHI2A plasmid belonging to plasmid multilocus sequence typing sequence type 1 in a region surrounded by chromosomal genes previously identified to be adjacent to blaOXA genes in Shewanella spp. In conclusion, OXA-436 is a novel CHDL with functional properties similar to those of OXA-48-like CHDLs. The described geographical spread among different Enterobacteriaceae and the plasmid location of blaOXA-436 illustrate its potential for further dissemination.

Original languageEnglish
Article numbere01260-17
JournalAntimicrobial Agents and Chemotherapy
Issue number1
Number of pages13
Publication statusPublished - Jan 2018

    Research areas

  • Carbapenems

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