Dissemination and Characteristics of a Novel Plasmid-Encoded Carbapenem-Hydrolyzing Class D {beta}-Lactamase, OXA-436 from Four Patients Involving Six Different Hospitals in Denmark [PublishAheadOfPrint]

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 carbapenemase (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 90.4-92.8% identity to 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 OXA-48 and OXA-181 with activity against penicillins including temocillin, limited or no activity against extended-spectrum cephalosporins and activity against carbapenems. The bla_OXA-436 gene was located on a conjugative ~314 kb IncHI2/IncHI2A plasmid belonging to pMLST ST1, in a region surrounded by chromosomal genes previously identified adjacent to bla_OXA-genes in Shewanella spp. In conclusion, OXA-436 is a novel CHDL with similar functional properties as OXA-48-like CHDLs. The described geographical spread among different Enterobacteriaceae and plasmid location of bla_OXA-436 illustrates its potential for further dissemination.

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