Reduced ceftazidime and ertapenem susceptibility due to production of OXA-2 in Klebsiella pneumoniae ST258. (24th May 2019)

• Record Type: Journal Article
• Authors: Iovleva, Alina; Mettus, Roberta T; McElheny, Christi L; Mustapha, Mustapha M; Van Tyne, Daria; Shields, Ryan K; Pasculle, A William; Cooper, Vaughn S; Doi, Yohei
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 74:Number 8(2019)
• Page Start: 2203
• Page End: 2208
• Publication Date: 2019-05-24
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkz183
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: OXA-2 is a class D β-lactamase that confers resistance to penicillins, as well as narrow-spectrum cephalosporins. OXA-2 was recently reported to also possess carbapenem-hydrolysing activity. Here, we describe a KPC-2-encoding Klebsiella pneumoniae isolate that demonstrated reduced susceptibility to ceftazidime and ertapenem due to production of OXA-2. Objectives: To elucidate the role of OXA-2 production in reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 clinical isolate. Methods: MICs were determined by the agar dilution method. WGS was conducted to identify and compare resistance genes between isolates. Expression of KPC-2 was quantified by quantitative RT–PCR and immunoblotting. OXA-2 was expressed in Escherichia coli TOP10, as well as in K. pneumoniae ATCC 13883, to define the relative contribution of OXA-2 in β-lactam resistance. Kinetic studies were conducted using purified OXA-2 enzyme. Results: K. pneumoniae 1761 belonged to ST258 and carried both bla KPC-2 and bla OXA-2 . However, expression of bla KPC-2 was substantially reduced due to an IS 1294 insertion in the promoter region. K. pneumoniae 1761, K. pneumoniae ATCC 13883 and E. coli TOP10 carrying bla OXA-2 -harbouring plasmids showed reduced susceptibility to ertapenem and ceftazidime, but meropenem, imipenem and cefepime were unaffected. bla OXA-2 was carried on a 2910 bp partial class 1 integron containing aacA4 - bla OXA-2 - qacEΔ1 - sul1 on an IncA/C2 plasmid, which was not present in the earlier ST258 isolates possessing bla KPC-2 with intact promoters. Hydrolysis of ertapenem by OXA-2 was confirmed using purified enzyme. Conclusions: Production of OXA-2 was associated with reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 isolate.