[A three-dimensional model for in vitro study of the association of three antibiotics. Application to the activity of piperacillin, tazobactam and amikacin against five strains of enterobacteria as a function of their phenotype of beta-lactam resistance]. / Modèle tridimensionnel pour l'étude in vitro de l'association de trois antibiotiques. Application à l'activité de pipéracilline, tazobactam et amikacine sur cinq souches d'entérobactéries en fonction de leur phénotype de résistance aux bêta-lactamines.

We described an in vitro 3-dimensional model to study the bactericidal activity of piperacillin (P), tazobactam (T) and amikacin (A) in combination against 5 strains of enterobacteria with different resistance patterns of beta-lactam antibiotics. A synergy was defined by calculation of sigma FBCP,T,A = BCp/MBCp + BCT/MBCT + BCA/MBCA and classic sigma FBCs for each double combination. The therapeutic value of each antibiotic was estimated by comparison of its bactericidal concentrations alone and in double or triple combination.

[In vitro antibacterial activity of piperacillin-tazobactam in combination with netilmicin or amikacin against Enterobacteriaceae resistant to amoxicillin]. / Activité antibactérienne in vitro de pipéracilline-tazobactam en association avec la nétilmicine ou l'amikacine sur des entérobactéries résistantes à l'amoxicilline.

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.