ANTIBACTERIAL IN-VITRO ACTIVITY OF PIPERA CILLIN-TAZOBACTAM IN COMBINATION WITH NETILMICIN OR AMIKACIN AGAINST AMOXICILLIN-RESISTANT STRAINS OF ENTEROBACTERIACEAE

The antibacterial in vitro activity of piperacillin and tazobactam (in a concentration ratio of 8/1) was studied in combination with netilmi cin or amikacin by a microtiter checkerboard assay against 162 strains of Enterobacteriaceae. These strains were selected for their resistan ce pattern to beta-lactam antibiotics and their beta-lactamases were c haracterized by the mean of isoelectric focusing in comparison with re ference strains. A comparison of the MICs of piperacillin, alone and i n combination, assessed the efficacy of tazobactam as beta-lactamase i nhibitor, particularly when a TEM-1 beta-lactamase was produced. When the strains were sensitive to the aminoglycosides(lll netilmicin-sensi tive ones and 131 amikacin-sensitive ones), we observed 55 % of synerg istic effects and 45 % of additions with the combinations piperacillin -tazobactam-netilmicin or amikacin. A synergistic effect was usually e ncountered with P. mirabilis, P. vulgaris, M, morganii and with the st rains off. coli, E. cloacae and S. marcescens which produced a cephalo sporinase only. Among the 51 strains that were intermediate or resista nt to netilmicin, 8 ones were inhibited by piperacillin-tazobactam-net ilmicin at therapeutic levels (3 synergisms, 5 additions). Among the 3 1 strains that were intermediate or resistant to amikacin, 24 ones (18 synergisms, 6 additions) were inhibited by piperacillin-tazobactam-am ikacin at therapeutic concentrations. In most of the cases, the combin ation of piperacillin-tazobactam with an aminoglycoside enhanced the a ntibacterial activity of these agents by decreasing the concentrations necessary to inhibit the strains.