title: In vivo selection of imipenem-resistant Klebsiella pneumoniae producing extended-spectrum beta-lactamase CTX-M-15 and plasmid-encoded DHA-1 cephalosporinase.
abstract: Four Klebsiella pneumoniae isolates (KP1-4) were recovered sequentially from an infected patient. Whilst KP1-3 were resistant to all beta-lactams except carbapenems, KP4 recovered after 24 days of imipenem-containing treatment showed additional resistance to carbapenems. No carbapenem hydrolysis could be identified in KP4. Molecular characterisation revealed that KP1-4 were indistinguishable by pulsed-field gel electrophoresis, contained a 95-kb self-transferable plasmid harbouring bla(CTXM-15) and bla(TEM-1) genes and a 65-kb plasmid that was not transferred by conjugation into Escherichia coli, and harboured the plasmid-mediated bla(DHA-1) AmpC beta-lactamase gene. In addition, KP4 failed to express OmpK36 owing to a point mutation leading to a premature stop of the protein. This study demonstrates development of carbapenem resistance related to loss of OmpK36 expression in a K. pneumoniae isolate harbouring extended-spectrum beta-lactamase and plasmid-mediated cephalosporinase genes following prolonged imipenem exposure.
authors.affiliation: Service de Bactériologie-Virologie, INSERM U914 Emerging Resistance to Antibiotics, Hôpital de Bicêtre, 94275 Le Kremlin-Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Cuzon
authors.forename: Thierry
authors.initials: T
authors.lastname: Naas
authors.forename: Michele
authors.initials: M
authors.lastname: Guibert
authors.forename: Patrice
authors.initials: P
authors.lastname: Nordmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015373:Bacterial Typing Techniques; D016172:DNA Fingerprinting; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D006801:Humans; D015378:Imipenem / Q000494:pharmacology* / Q000627:therapeutic use; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D010957:Plasmids; D012641:Selection, Genetic; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D015378:Imipenem; D001618:beta-Lactamases