Identification of DHA-23, a novel plasmid-mediated and inducible AmpC beta-lactamase from Enterobacteriaceae in Northern Taiwan.

Objectives: AmpC beta-lactamases are classified as Amber Class C and Bush Group 1. AmpC beta-lactamases can hydrolyze broad and extended-spectrum cephalosporins, and are not inhibited by beta-lactamase inhibitors such as clavulanic acid. This study was conducted to identify DHA-23, a novel plasmid-mediated and inducible AmpC beta-lactamase obtained from Enterobacteriaceae. Methods: A total of 210 carbapenem-resistant Enterobacteriaceae isolates were collected from a medical center (comprising two branches) in Northern Taiwan during 2009-2012. AmpC beta-lactamase genes were analyzed through a polymerase chain reaction using plasmid DNA templates and gene sequencing. The genetic relationships of the isolates were typed using pulsed field gel electrophoresis following the digestion of intact genomic DNA by using XbaI. Results: Three enterobacterial isolates (one Escherichia coli and two Klebsiella pneumoniae) were obtained from three hospitalized patients. All three isolates were resistant or intermediate lysusceptible to all beta-lactams, and exhibited reduced susceptibility to carbapenems. These three isolates expressed a novel AmpC beta-lactamase, designated DHA-23, approved by the curators of the Lahey website. DHA-23 differs from DHA-1 and DHA-6 by one amino acid substitution (Ser245Ala), exhibiting three amino acid changes compared with DHA-7 and DHA-Morganella morganii; three amino acid changes compared with DHA-3; four amino acid changes compared with DHA-5; and eight amino acid changes compared with DHA-2(>97% identity). This AmpC beta-lactamase is inducible using a system involving ampR. Conclusion: This is the first report to address DHA-23, a novel AmpC beta-lactamase. DHA-type beta-lactamases are continuous threat in Taiwan.