[Meropenem against bacteria carriers of wide spectrum TEM beta-lactamases: evolutive aspects].
The so-called wide spectrum beta-lactamases (WSBLs) are able to hydrolyze wide spectrum cephalosporins or monobactamics such as cefotaxime, ceftriaxone, ceftazidime, cefepime, cefpiroma or aztreonam. The natural wide spectrum beta-lactamases are mutational variants of TEM-1 consisting in the substitution of one of more amino acids within seven well defined positions in the molecule. Given the expected extremely low frequency for the simultaneous production of double or triple mutations, it is plausible that one of the mutational changes has been independently selected. A plurimutational remodelling of the TEM-beta-lactamase molecule is successively produced with the consequent appearance of highly effective ESBLs. Mutagenesis techniques allow clean molecular variants to be produced and allow the mutational effects under homogeneous conditions of bacterial strain, the plasmid implicated or the genic promotor to be studied. Meropenem remains active versus all the wide spectrum beta-lactamases referred in the 2be group of Bush, Jacoby and Medeiros as well as the new beta-lactamases produced in vitro by directed mutagenesis.
Baquero
F
F
Servicio de Microbiología, Hospital Ramón y Cajal, Madrid.
Morosini
M I
MI
Negri
M C
MC
Cantón
R
R
Blázquez
J
J
D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D017354:Point Mutation; D013845:Thienamycins / Q000378:metabolism / Q000494:pharmacology*; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
D013845:Thienamycins; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; C056342:beta-lactamase TEM-2; D000077731:Meropenem