title: Factors determining resistance to beta-lactam combined with beta-lactamase inhibitors in Escherichia coli.
abstract: The influence of inoculum size, beta-lactamase hyperproduction (multicopy plasmid) and modifications in the outer membrane protein profile on the susceptibility of Escherichia coli to combinations of amoxycillin/clavulanate, amoxycillin/sulbactam, amoxycillin/tazobactam and piperacillin/tazobactam were studied. For all combinations the bacterial susceptibility was affected by factors determining an increase in beta-lactamase (inoculum size or hyperproduction). Clavulanic acid was the most efficient beta-lactamase inhibitor. The absence of the outer membrane proteins, OmpF and OmpC, did not significantly affect susceptibility to the combinations per se but when combined with the presence of beta-lactamase high MICs were observed. Seven out of eight amoxycillin/clavulanate resistant clinical isolates of E. coli had beta-lactamase hyperproduction and a decrease or absence of OmpF.
authors.affiliation: Servicio de Microbiología, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Reguera
authors.forename: F
authors.initials: F
authors.lastname: Baquero
authors.forename: J C
authors.initials: JC
authors.lastname: Pérez-Díaz
authors.forename: J L
authors.initials: JL
authors.lastname: Martínez
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology; D019980:Amoxicillin-Potassium Clavulanate Combination; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000235:genetics*; D002463:Cell Membrane Permeability; D002969:Clavulanic Acids / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D000078142:Tazobactam; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D002969:Clavulanic Acids; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin; D010397:Penicillanic Acid; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; D000078142:Tazobactam; D010878:Piperacillin