OXA-427, a new plasmid-borne carbapenem-hydrolysing class D β-lactamase in Enterobacteriaceae

J Antimicrob Chemother. 2017 Sep 1;72(9):2469-2477. doi: 10.1093/jac/dkx184.

Abstract

Objectives: To describe a novel plasmid-borne class D carbapenemase (CHDL) named OXA-427 identified in several Enterobacteriaceae clinical isolates from nine patients in one Belgian hospital.

Methods: OXA-427-producing isolates were analysed by an electrochemical imipenem hydrolysis method (BYG Carba test), Carba NP test, conventional phenotypic assays and by molecular methods (PCR, whole sequencing of the OXA-427-encoding plasmid and cloning). The antimicrobial resistance profile of OXA-427 was analysed by expression of the cloned gene in Escherichia coli DH10B and J53.

Results: Eleven OXA-427-producing Enterobacteriaceae isolates of various species were identified from clinical specimens of nine patients between March 2012 and June 2014. OXA-427 shares only 22%-29% amino acid identity with OXA-48-like enzymes and other acquired CHDL (e.g. OXA-23, -24/40 and -58 of Acinetobacter spp.). Conversely, it appeared closely related to the chromosomal class D β-lactamase of Aeromonas media, Aeromonas hydrophila and Aeromonas sobria (99%, 89% and 77% of identity, respectively). When expressed in E. coli, OXA-427 hydrolysed imipenem and conferred resistance to extended-spectrum cephalosporins (mostly ceftazidime), penicillins including temocillin, and reduced susceptibility to carbapenems. The blaOXA-427 gene was located in a 45 kb resistance island on a 177 kb IncA/C plasmid.

Conclusions: OXA-427 is a novel CHDL most closely related to chromosomal class D β-lactamase of A. media WS. It confers resistance to penicillins, ceftazidime and aztreonam and in some instances to carbapenems. OXA-427, which is not detectable by classical molecular tests, caused a protracted outbreak in one university hospital over a 2 year period.

Publication types

  • Case Reports

MeSH terms

  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / isolation & purification
  • Bacterial Proteins / metabolism*
  • Belgium / epidemiology
  • Carbapenems / metabolism*
  • Carbapenems / pharmacology
  • Cloning, Molecular
  • Drug Resistance, Multiple, Bacterial / genetics
  • Enterobacteriaceae / enzymology*
  • Enterobacteriaceae Infections / epidemiology
  • Enterobacteriaceae Infections / microbiology*
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Hydrolysis
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Plasmids / genetics*
  • beta-Lactamases / genetics*
  • beta-Lactamases / isolation & purification
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • beta-Lactamases
  • carbapenemase