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

Klebsiella pneumoniae BM2974 isolated from an abdominal abcess was resistan t to high concentrations of all available beta -lactams, including recently developed third-generation cephalosporins and carbapenems. Isoelectric foc using of beta -lactamases and amplification, cloning and sequencing of the corresponding genes, together with conjugation and transformation experimen ts, indicated that, in addition to the chromosomally encoded beta -lactamas e, the strain produced three plasmid-mediated beta -lactamases with pls of 5.4, 8.2 and 9.0, which corresponded to TEM-1, SHV-5 and AmpC-type CMY-4, r espectively. Strain BM2974 also tacked 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 attribut able to production of CMY-4 beta -lactamase combined with permeability alte ration.