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

Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01260-17. doi: 10.1128/AAC.01260-17. Print 2018 Jan.


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.

Keywords: carbapenems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism*
  • Carbapenems / pharmacokinetics
  • Denmark
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / genetics*
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / microbiology*
  • Humans
  • Hydrolysis
  • Microbial Sensitivity Tests
  • Plasmids / genetics
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism*


  • Bacterial Proteins
  • Carbapenems
  • beta-Lactamases
  • carbapenemase