Emergence of Oxacillinase-mediated Resistance to Imipenem in Klebsiella Pneumoniae

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2003 Dec 25

PMID 14693513

Citations 401

Authors

Laurent Poirel

Claire Heritier

Venus Tolun

Patrice Nordmann

Affiliations

Soon will be listed here.

Abstract

Klebsiella pneumoniae strain 11978 was isolated in Turkey in 2001 and was found to be resistant to all beta-lactams, including carbapenems. Cloning and expression in Escherichia coli identified five beta-lactamases, including two novel oxacillinases. The beta-lactamase OXA-48 hydrolyzed imipenem at a high level and was remotely related (less than 46% amino acid identity) to the other oxacillinases. It hydrolyzed penicillins and imipenem but not expanded-spectrum cephalosporins. The bla(OXA-48) gene was plasmid encoded and not associated with an integron, in contrast to most of the oxacillinase genes. An insertion sequence, IS1999, was found immediately upstream of bla(OXA-48). Another plasmid that encoded a second oxacillinase gene, bla(OXA-47), located inside a class 1 integron was identified in K. pneumoniae 11978. OXA-47 had a narrow spectrum of hydrolysis activity and did not hydrolyze ceftazidime or imipenem, as is found for the beta-lactamase (OXA-1) to which it is related. In addition, beta-lactamases TEM-1 and SHV-2a were expressed from the same K. pneumoniae isolate. Analysis of the outer membrane proteins of this isolate revealed that it lacked a porin of ca. 36 kDa. Thus, the high-level resistance to beta-lactams of this clinical isolate resulted from peculiar beta-lactamases and modification of outer membrane proteins.

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