title: 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.
authors: Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15, France.
authors: V T
authors: VT
authors: Cao
authors: G
authors: G
authors: Arlet
authors: B M
authors: BM
authors: Ericsson
authors: A
authors: A
authors: Tammelin
authors: P
authors: P
authors: Courvalin
authors: T
authors: T
authors: Lambert
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D001426:Bacterial Proteins; D003227:Conjugation, Genetic; D004352:Drug Resistance, Microbial; D015378:Imipenem / Q000494:pharmacology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D013845:Thienamycins / Q000494:pharmacology*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D013845:Thienamycins; D015378:Imipenem; C048795:AmpC beta-lactamases; D001618:beta-Lactamases