哌拉西林/舒巴坦的药效学研究

Study on the activities of pipercillin/sulbactam in vitro and in vivo

目的 研究哌拉西林 /舒巴坦及哌拉西林对临床分离菌的体外抗菌及体内保护作用。方法 采用平皿二倍稀释法测定最低抑菌浓度 (MIC) ;采用试管二倍稀释法测定最低杀菌浓度 (MBC)及杀菌试验 ;采用腹腔感染后经皮下注射药物测定对小鼠的半数保护剂量 (ED50 )。结果 哌拉西林 /舒巴坦对产酶革兰阴性需氧菌及厌氧菌的体外抗菌活性均高于哌拉西林和氨苄西林 /舒巴坦 ;哌拉西林与舒巴坦的不同配比对其抗菌活性影响不大 ;哌拉西林 /舒巴坦对临床常见产酶菌的MIC和MBC非常接近。细菌接种量在 10 4～ 10 7CFU·mL-1、培养基在 pH6 .0～ 8.0及蛋白含量在 2 5 %～ 75 %时 ,对哌拉西林 /舒巴坦的体外抗菌活性无明显影响。哌拉西林 /舒巴坦各配比与单用哌拉西林相比 ,相对水解率均有非常显著差异 (P <0 .0 1) ;产 β内酰胺酶的金黄色葡萄球菌、产头孢菌素酶的变形杆菌以及产超广谱 β内酰胺酶的大肠埃希菌和肺炎克雷白菌分别感染小鼠 ,哌拉西林 /舒巴坦 2∶1和 4∶1配比均能明显提高哌拉西林的疗效。结论 哌拉西林 /舒巴坦有较好的稳定性 ,对临床常见产酶菌显示出了较强的抗菌活性 ,哌拉西林 /舒巴坦的体外抗菌活性与体内保护效果是平行的。

OBJECTIVE: The in vitro and in vivo activities of pipercillin/sulbactam (PIPC/SBT) were compared with those of pipercillin against some clinical isolates. METHODS: The minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations(MBC) of the isolates were detected by agar dilution and broth dilution. The mean effective dose(ED50) were detected by the mice with systemic infection. RESULTS: Against most of gram-negative bacteria and anaerobe, pipercillin/sulbactam showed stronger activity than that of ampicillin/sulbactam(AMP/SBT) and pipercillin. Sulbactam, a β-lactamases inhibitor, when combined with pipercillin showed a synergistic antibacterial activity with a more potent therapeutic effect than PIPC alone in mice with systemic infection caused by β-lactamases-producing strains. The relative hydrolysis rate of pipercillin/sulbactam was lower than that of pipercillin alone. CONCLUSION: Combined pipercillin with sulbactam was more stable to β-lactamases-producing bacteria than pipercillin alone.