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Journal of Antimicrobial Chemotherapy (2000) 46, 895-900
© 2000 The British Society for Antimicrobial Chemotherapy

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

Van Thi Bao Caoa, Guillaume Arletb, Britt-Marie Ericssonc, Ann Tammelinc, Patrice Courvalina and Thierry Lamberta,d,*

a Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15, France; b Service de Bactériologie, Hôpital Tenon, 75970 Paris Cedex 20, France; c University Hospital, Uppsala, Sweden; d Centre d'Etude Pharmaceutiques, Châtenay–Malabry, France

Klebsiella pneumoniae BM2974 isolated from an abdominal abcess was resistant to high concentrations of all available ß-lactams, including recently developed third-generation cephalosporins and carbapenems. Isoelectric focusing of ß-lactamases and amplification, cloning and sequencing of the corresponding genes, together with conjugation and transformation experiments, indicated that, in addition to the chromosomally encoded ß-lactamase, the strain produced three plasmid-mediated ß-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 ß-lactamase combined with permeability alteration.

* Corresponding author. Tel: +33-1-45-68-83-21; Fax: +33-1-45-68-83-19; E-mail: tlambert{at}pasteur.fr


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