Muratani T, Yokota E, Nakane T, Inoue E, Mitsuhashi S
Episome Institute, Gunma, Japan.
J Antimicrob Chemother. 1993 Sep;32(3):421-9. doi: 10.1093/jac/32.3.421.
The in-vitro synergic activities of BRL42715, a new beta-lactamase inhibitor, clavulanic acid, sulbactam, and tazobactam combined with ampicillin, piperacillin, cephalothin, or cefoperazone were tested against various bacteria producing known types of beta-lactamase. BRL42715 showed the best synergistic activity among the inhibitors tested against strains producing penicillinases of type I, II, III, V, and that from Klebsiella pneumoniae, cephalosporinases, and oxyiminocephalosporinases (except that from Klebsiella oxytoca). Clavulanic acid combined with the beta-lactams tested showed the best synergic activity of the inhibitors against strains producing type IV penicillinase and oxyiminocephalosporinase from K. oxytoca. The 50% inhibitory doses of BRL42715 were superior to those of clavulanic acid against various types of beta-lactamases except for type IV penicillinase and the oxyiminocephalosporinase from K. oxytoca. The inhibitory activity of BRL42715 against cephalosporinases from various bacteria was 10(4) to 10(6)-fold greater than that of clavulanic acid. The synergic effects of BRL42715 and clavulanic acid on the activity of piperacillin were compared against six clinical isolates of bacteria resistant to piperacillin. The synergic activity of BRL42715 was greater than that of clavulanic acid in all six isolates.
对新型β-内酰胺酶抑制剂BRL42715、克拉维酸、舒巴坦和他唑巴坦分别与氨苄西林、哌拉西林、头孢噻吩或头孢哌酮联合应用时，针对产生已知类型β-内酰胺酶的各种细菌进行了体外协同活性测试。在针对产生I型、II型、III型、V型青霉素酶的菌株以及肺炎克雷伯菌、头孢菌素酶和氧亚氨基头孢菌素酶（除产酸克雷伯菌外）的菌株所测试的抑制剂中，BRL42715显示出最佳的协同活性。克拉维酸与所测试的β-内酰胺联合应用时，在针对产IV型青霉素酶和产酸克雷伯菌的氧亚氨基头孢菌素酶的菌株的抑制剂中显示出最佳的协同活性。除了IV型青霉素酶和产酸克雷伯菌的氧亚氨基头孢菌素酶外，BRL42715对各种类型β-内酰胺酶的50%抑制剂量优于克拉维酸。BRL42715对各种细菌的头孢菌素酶的抑制活性比对克拉维酸的抑制活性高10^4至10^6倍。针对六株对哌拉西林耐药的临床分离菌，比较了BRL42715和克拉维酸对哌拉西林活性的协同作用。在所有六株分离菌中，BRL42715的协同活性均高于克拉维酸。
