title: [In vitro antibacterial activity of piperacillin-tazobactam in combination with netilmicin or amikacin against Enterobacteriaceae resistant to amoxicillin].
abstract: The antibacterial in vitro activity of piperacillin and tazobactam (in a concentration ratio of 8/1) was studied in combination with netilmicin or amikacin by a microtiter checkerboard assay against 162 strains of Enterobacteriaceae. These strains were selected for their resistance pattern to beta-lactam antibiotics and their beta-lactamases were characterized by the mean of isoelectric focusing in comparison with reference strains. A comparison of the MICs of piperacillin, alone and in combination, assessed the efficacy of tazobactam as beta-lactamase inhibitor, particularly when a TEM-1 beta-lactamase was produced. When the strains were sensitive to the aminoglycosides (111 netilmicin-sensitive ones and 131 amikacin-sensitive ones), we observed 55% of synergistic effects and 45% of additions with the combinations piperacillin-tazobactam-netilmicin or amikacin. A synergistic effect was usually encountered with P. mirabilis, P. vulgaris, M. morganii and with the strains of E. coli, E. cloacae and S. marcescens which produced a cephalosporinase only. Among the 51 strains that were intermediate or resistant to netilmicin, 8 ones were inhibited by piperacillin-tazobactam-netilmicin at therapeutic levels (3 synergisms, 5 additions). Among the 31 strains that were intermediate or resistant to amikacin, 24 ones (18 synergisms, 6 additions) were inhibited by piperacillin-tazobactam-amikacin at therapeutic concentrations. In most of the cases, the combination of piperacillin-tazobactam with an aminoglycoside enhanced the antibacterial activity of these agents by decreasing the concentrations necessary to inhibit the strains.
authors.affiliation: Service de Bactériologie Médicale, CHU Le Bocage, Dijon, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Duez
authors.forename: E
authors.initials: E
authors.lastname: Siebor
authors.forename: A
authors.initials: A
authors.lastname: Pechinot
authors.forename: X
authors.initials: X
authors.lastname: Cordin
authors.forename: C
authors.initials: C
authors.lastname: Chamard-Neuwirth
authors.forename: A
authors.initials: A
authors.lastname: Kazmierczak
mesh_terms: D000583:Amikacin / Q000494:pharmacology*; D000658:Amoxicillin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology; D004755:Enterobacteriaceae / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D009428:Netilmicin / Q000494:pharmacology*; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology*; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D009428:Netilmicin; D000658:Amoxicillin; D000583:Amikacin; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin
vernacular_title: Activité antibactérienne in vitro de pipéracilline-tazobactam en association avec la nétilmicine ou l'amikacine sur des entérobactéries résistantes à l'amoxicilline.