title: CMT-type beta-lactamase TEM-125, an emerging problem for extended-spectrum beta-lactamase detection.
abstract: The clinical strain Escherichia coli TO799 was resistant to penicillin-clavulanate combinations and ceftazidime and was not reproducibly detected as an extended-spectrum beta-lactamase (ESBL) according to the standards of the Clinical Laboratory Standards Institute (CLSI; formerly NCCLS) and the national guidelines of the French Society for Microbiology (Comité de l'Antibiogramme de la Société Française de Microbiologie). A novel beta-lactamase, designated TEM-125, was responsible for this phenotype. TEM-125 harbors a complex association of mutations previously described in the ESBL TEM-12 and in the inhibitor-resistant beta-lactamase TEM-39. TEM-125 is the first complex mutant TEM to present hydrolytic activity against ceftazidime (kcat, 3.7 s(-1)) together with a high level of resistance to clavulanate (50% inhibitory concentration, 13.6 microM). The discovery of such an ESBL, which is difficult to detect by the usual ESBL detection methods, confirms the emergence of a complex mutant TEM subgroup and highlights the need to evaluate detection methods so as to avoid possible therapeutic failures.
authors.affiliation: CHU Clermont-Ferrand, Laboratoire de Bactériologie, Faculté de Médecine, 63 001 Clermont-Ferrand, France. frobin@chu-clermontferrand.fr
authors.forename: Frédéric
authors.initials: F
authors.lastname: Robin
authors.forename: Julien
authors.initials: J
authors.lastname: Delmas
authors.forename: Maryse
authors.initials: M
authors.lastname: Archambaud
authors.forename: Cédric
authors.initials: C
authors.lastname: Schweitzer
authors.forename: Catherine
authors.initials: C
authors.lastname: Chanal
authors.forename: Richard
authors.initials: R
authors.lastname: Bonnet
mesh_terms: D019943:Amino Acid Substitution; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D006801:Humans; D007525:Isoelectric Focusing; D008826:Microbial Sensitivity Tests / Q000379:methods; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000145:classification* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination; D002442:Ceftazidime; D001618:beta-Lactamases