Emergence of imipenem resistance in Klebsiella pneumoniae owing to combination of plasmid-mediated CMY-4 and permeability alteration

Abstract

Klebsiella pneumoniae BM2974 isolated from an abdominal abcess was resistant to high concentrations of all available beta-lactams, including recently developed third-generation cephalosporins and carbapenems. Isoelectric focusing of beta-lactamases and amplification, cloning and sequencing of the corresponding genes, together with conjugation and transformation experiments, indicated that, in addition to the chromosomally encoded beta-lactamase, the strain produced three plasmid-mediated beta-lactamases with pIs of 5.4, 8.2 and 9.0, which corresponded to TEM-1, SHV-5 and AmpC-type CMY-4, respectively. Strain BM2974 also lacked a major outer membrane protein of c. 40 kDa which was present in the spontaneous imipenem-susceptible revertant BM2974-1. We suggest that imipenem resistance in strain BM2974 is attributable to production of CMY-4 beta-lactamase combined with permeability alteration.