Payne D J, Cramp R, Winstanley D J, Knowles D J
SmithKline Beecham Pharmaceuticals, Betchworth, Surrey, United Kingdom.
Antimicrob Agents Chemother. 1994 Apr;38(4):767-72. doi: 10.1128/AAC.38.4.767.
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.
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，这三种抑制剂对多种不同质粒介导的β-内酰胺酶的抑制数据尚未在相同实验条件下进行比较。许多研究小组推断克拉维酸可抑制超广谱TEM和SHVβ-内酰胺酶，但相关抑制数据很少发表。在本研究中，已测定了这三种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。另外15种酶是常规谱β-内酰胺酶，如TEM-1和SHV-1。对于所测试的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的抑制效力分别比舒巴坦高60倍和580倍，而TEM-1和SHV-1是目前临床上最常见的两种革兰氏阴性质粒介导的β-内酰胺酶。对50%抑制浓度数据的统计分析表明，总体而言，克拉维酸对常规谱酶的活性比舒巴坦高20倍。此外，克拉维酸在抑制超广谱酶方面比舒巴坦强14倍。他唑巴坦对两组β-内酰胺酶的活性也明显高于舒巴坦。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之间没有显著差异，尽管观察到它们的抑制谱有所不同。
