头孢哌酮和哌拉西林与β内酰胺酶抑制剂对大肠埃希菌和肺炎克雷伯菌的后效应研究

PAE, PLIE and PASME of β-Lactams/β-Lactamase inhibitors against β-Lactamase-producing E.coli and K.pneumonia

目的测定头孢哌酮和哌拉西林与克拉维酸、舒巴坦、三唑巴坦3种β内酰胺酶抑制剂的不同复方的最低抑菌浓度(MIC)、抗生素后效应(PAE)、β内酰胺酶抑制剂后效应(PLIE)和亚抑菌浓度后效应(PASME)。方法以肉汤稀释法测定MIC;以菌落计数法测定菌落形成单位(CFU),根据CFU做生长曲线,计算PAE、PLIE、PASME。结果不同比例复方对产β内酰胺酶菌株的MIC较单方呈2～256倍的降低。无论单方还是复方均无长PAE。3种β内酰胺酶抑制剂的PLIE对于大肠埃希菌有正有负(-2.25h～>5h),而对于肺炎克雷伯菌均为正值(0.34h～5.37h)。对于肺炎克雷伯菌,0.2MIC的头孢哌酮/舒巴坦(1/1)的PASME为0.32h,0.1MIC、0.2MIC的哌拉西林/克拉维酸(8/1)的PASME分别为2.96h、4.41h。结论同时具有长PLIE及PASME的复方,PLIE、PASME较其半衰期在给药方案的设计中更为重要;PAE、PLIE、PASME作为重要的药效动力学参数,可应用于评价新抗菌药物的药效学和优化给药方案。

Objectives To measure the minimal inhibitory concentration （MIC）, post antibiotic effect（PAE）, post β-lactamase inhibitor effect （PLIE） and post antibiotic sub-MIC effect （PASME） of combinations of β-lactams and β-lactamase inhibitors against β-lactamase-producing gram-negative bacteria in vitro. Methods MICs were detected by broth macrodilution method. The numbers of CFU on plates were counted. The growth curves of the bacteria were drawn according to CFU counts, therefore PAEs, PLIEs and PASMEs were calculated by the curves. Results MICs of the combinations were 2 - 256 times lower than those of β-lactams alone. No longer PAE was found in the combinations of β-lactam/βlactamase inhibitor or β-lactam alone. PLIEs induced by β-lactamase inhibitors were - 2. 25 h - 〉 5 h on E. coli and O. 34 h - 5. 37 h on K. pneumonia, respectively. A PASME of 0. 32h was found for cefoperazone/sulbactam（0. 2 times MIC）, and 2. 96 h, 4. 41 h for Piperacillin/Clavulanic acid（0. 1, 0. 2 times MIC） against K. pneumonia, respectively. Conclusions As for the combinations with both longer PLIE and PASME, the two parameters are more important than the half-times in the administration of dosage regimen. PAE, PLIE and PASME provide useful data for the evaluation of the new antibiotics and the determination of the optimal dosing regimen.