Duez J M, Siebor E, Pechinot A, Cordin X, Chamard-Neuwirth C, Kazmierczak A
Service de Bactériologie Médicale, CHU Le Bocage, Dijon, France.
Pathol Biol (Paris). 1995 Mar;43(3):208-14.
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.
采用微量滴定棋盘法，研究了哌拉西林与他唑巴坦（浓度比为8/1）联合奈替米星或阿米卡星对162株肠杆菌科细菌的体外抗菌活性。这些菌株根据其对β-内酰胺类抗生素的耐药模式进行选择，通过等电聚焦法与参考菌株比较，对其β-内酰胺酶进行了鉴定。比较了哌拉西林单独使用及联合使用时的最低抑菌浓度（MIC），评估了他唑巴坦作为β-内酰胺酶抑制剂的疗效，尤其是在产生TEM-1β-内酰胺酶的情况下。当菌株对氨基糖苷类敏感时（111株对奈替米星敏感，131株对阿米卡星敏感），我们观察到哌拉西林-他唑巴坦-奈替米星或哌拉西林-他唑巴坦-阿米卡星联合使用时，55%出现协同作用，45%出现相加作用。奇异变形杆菌、普通变形杆菌、摩根摩根菌以及仅产生头孢菌素酶的大肠埃希菌、阴沟肠杆菌和粘质沙雷氏菌菌株通常会出现协同作用。在对奈替米星中度或耐药的51株菌株中，有8株在治疗水平下被哌拉西林-他唑巴坦-奈替米星抑制（3例协同作用，5例相加作用）。在对阿米卡星中度或耐药的31株菌株中，有24株（18例协同作用，6例相加作用）在治疗浓度下被哌拉西林-他唑巴坦-阿米卡星抑制。在大多数情况下，哌拉西林-他唑巴坦与氨基糖苷类联合使用可通过降低抑制菌株所需的浓度来增强这些药物的抗菌活性。
