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

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.

Author information

1
Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway.
2
Microbial Pharmacology and Population Biology Research Group, Department of Pharmacy, UiT, The Arctic University of Norway, Tromsø, Norway.
3
Department of Bacteria, Parasites, and Fungi, Statens Serum Institut, Copenhagen, Denmark.
4
The Norwegian Structural Biology Centre (NorStruct), Department of Chemistry, UiT, The Arctic University of Norway, Tromsø, Norway.
5
Research Group on Host-Microbe Interactions, Department of Medical Biology, UiT, The Arctic University of Norway, Tromsø, Norway.
6
Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark.
7
Department of Clinical Microbiology, Slagelse Hospital, Slagelse, Denmark.
8
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
9
Pathogen Genomics Division, Translational Genomics Research Institute (TGen), Flagstaff, Arizona, USA.
10
Veterinary Disease Biology, University of Copenhagen, Copenhagen, Denmark.
11
Department of Bacteria, Parasites, and Fungi, Statens Serum Institut, Copenhagen, Denmark ama@ssi.dk.

Abstract

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

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