COMPARATIVE ACTIVITIES OF CLAVULANIC ACID, SULBACTAM, AND TAZOBACTAM AGAINST CLINICALLY IMPORTANT BETA-LACTAMASES
COMPARATIVE ACTIVITIES OF CLAVULANIC ACID, SULBACTAM, AND TAZOBACTAM AGAINST CLINICALLY IMPORTANT BETA-LACTAMASES
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DOI：
10.1128/aac.38.4.767
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发表时间：
1994-04-01
影响因子：
4.9
通讯作者：
KNOWLES, DJC
中科院分区：
文献类型：
--
作者：
PAYNE, DJ;CRAMP, R;KNOWLES, DJC
克拉维酸、舒巴坦和他唑巴坦是多种质粒介导的 β-内酰胺酶的抑制剂。然而，这三种抑制剂与多种不同质粒介导的β-内酰胺酶的抑制数据尚未在相同的实验条件下进行比较。许多研究小组推测克拉维酸可抑制超广谱 TEM 和 SHV β-内酰胺酶，但抑制数据很少发表。在这项研究中，已经确定了这三种β-内酰胺酶抑制剂对35种质粒介导的β-内酰胺酶的50%抑制浓度。在这 35 种 β-内酰胺酶中，20 种是超广谱 TEM 或 SHV 衍生的 β-内酰胺酶。其他 15 种酶是常规谱 β-内酰胺酶，例如 TEM-1 和 SHV-1。对于测试的 35 种质粒介导的 β-内酰胺酶中的 32 种，克拉维酸是比舒巴坦更有效的抑制剂。特别是，克拉维酸对 TEM-1 和 SHV-1（目前临床上最流行的两种革兰氏阴性质粒介导的 β-内酰胺酶）的效力分别比舒巴坦强 60 倍和 580 倍。对50%抑制浓度数据的统计分析表明，克拉维酸对常规谱酶的总体活性比舒巴坦高20倍。此外，克拉维酸对超广谱酶的抑制作用比舒巴坦强 14 倍。他唑巴坦对两组 β-内酰胺酶的活性也显着高于舒巴坦。他唑巴坦和克拉维酸对超广谱 TEM 和 SHV 酶以及常规谱酶的总体活性没有显着差异，尽管观察到它们的抑制谱存在差异。
Clavulanic acid, sulbactam, and tazobactam are inhibitors of a variety of plasmid-mediated beta-lactamases. However, inhibition data for these three inhibitors with a wide range of different plasmid-mediated beta-lactamases have not yet been compared under the same experimental conditions. A number of groups have inferred that clavulanic acid inhibits extended-spectrum TEM and SHV beta-lactamases, but inhibition data have rarely been published. In this study, the 50% inhibitory concentrations of these three beta-lactamase inhibitors for 35 plasmid-mediated beta-lactamases have been determined. Of these 35 beta-lactamases, 20 were extended-spectrum TEM- or SHV-derived beta-lactamases. The other 15 enzymes were conventional-spectrum beta-lactamases such as TEM-1 and SHV-1. Clavulanic acid was a more potent inhibitor than sulbactam for 32 of the 35 plasmid-mediated beta-lactamases tested. In particular, clavulanic acid was 60 and 580 times more potent than sulbactam against TEM-1 and SHV-1, respectively, currently the two most clinically prevalent gram-negative plasmid-mediated beta-lactamases. Statistical analysis of the data of the 50% inhibitory concentrations showed that clavulanic acid was 20 times more active overall than sulbactam against the conventional-spectrum enzymes. In addition, clavulanic acid was 14 times more potent than sulbactam at inhibiting the extended-spectrum enzymes. Tazobactam also showed significantly greater activity than sulbactam against the two groups of beta-lactamases. There were no significant differences between the overall activities of tazobactam and clavulanic acid against the extended-spectrum TEM and SHV enzymes and conventional-spectrum enzymes, although differences in their inhibition profiles were observed.