注射用头孢噻肟钠他唑巴坦钠的体外抗菌活性研究

目的研究头孢噻肟钠他唑巴坦钠复方制剂对产β-内酰胺酶的头孢噻肟耐药最小抑菌浓度(MIC)≥64μg/ml]临床分离菌的体外抗菌活性。方法采用琼脂二倍稀释法测定了不同配比头孢噻肟钠他唑巴坦钠复方制剂(CTX/TAZ1∶1、2∶1、4∶1、8∶1、16∶1)的体外MIC值,并与哌拉西林钠他唑巴坦钠(PIP/TAZ8∶1)、头孢哌酮钠舒巴坦钠(CPZ/SBT1∶1)进行比较。结果与头孢噻肟钠单独用药相比,头孢噻肟钠他唑巴坦钠复方制剂对产酶的大肠埃希菌、肺炎克雷伯杆菌、醋酸钙不动杆菌、阴沟肠杆菌、产气肠杆菌、黏质沙雷菌和异型枸橼酸杆菌的抗菌活性明显增强,MIC50至单用头孢噻肟钠的1/2～1/64。头孢噻肟钠他唑巴坦钠复方制剂对产酶的甲氧西林耐药金黄色葡萄球菌(MRSA)、甲氧西林耐药表皮葡萄球菌(MRSE)、铜绿假单胞菌的抗菌活性没有明显影响,MIC50不变或降低至1/2。他唑巴坦钠对头孢噻肟抗菌活性的增强作用随着他唑巴坦钠的加入量增加而增强,其中CTX/TAZ4∶1对大肠埃希菌(包括产超广谱β-内酰胺酶ESBLs)、肺炎克雷伯杆菌(包括产ESBLs)、醋酸钙不动杆菌、阴沟肠杆菌、产气肠杆菌、黏质沙雷菌和异型枸橼酸杆菌的MIC50分别为4、4、64、32、8、4和8μg/ml,其抗菌活性比CTX单独用药高,MIC50为单独用药的1/4～1/32。头孢噻肟/他唑巴坦4∶1对大肠埃希菌、肺炎克雷伯杆菌的抗菌活性优于哌拉西林/他唑巴坦、头孢哌酮/舒巴坦,MIC50为后两种组合的1/4～1/8。头孢噻肟/他唑巴坦4∶1对醋酸钙不动杆菌、阴沟肠杆菌、异型枸橼酸杆菌、产气肠杆菌和黏质沙雷菌的抗菌活性稍强于哌拉西林/他唑巴坦,弱于或接近于头孢哌酮/舒巴坦。结论他唑巴坦钠的加入可以有效增强头孢噻肟对除MRSA、MRSE和铜绿假单胞菌外的受试菌的敏感性。

In vitro antibacterial activity of Cefotaxime/Tazobactam combination

Objective To investigate the in vitro antibacterial activity of Cefotaxime/Tazobactam combination against β-1aetamase-producing Cefotaxime-resistant clinical isolates （MIC 1〉 64 μg/ml）. Methods The MICs of different Cefotaxime/Tazobactam combinations （CTX/TAZ 1：1, 2：1, 4：1, 8：1 and 16：1） were determined by agar dilution method, and were compared to those of Piperacillin/Tazobactam （8：1） and Cefoperazone/Sulbactam （1：1）. Results In comparison to Cefotaxime alone, Cefotaxime/Tazobactam showed increased antibacterial activity against 13-1actamase-produeing E. coli, K. pneumoniae, A. calcoaceticus, E. cloacae, E. aerogenes, S. marceseens and C. diversus. The MIC50s of different Cefotaxime/Tazobactam combinations were 2-64 folds lower than those of Cefotaxime. As to β-1actamase-producing MRSA, MRSE and P. aeruginosa, adding of Tazobactam did not exhibit obvious effects on the antibacterial activity of Cefotaxime, and MICas of Cefotaxime/Tazobactam were similar to those of Cefotaxime, or two folds lower. The antibacterial activity of Cefotaxime/Tazobactam combination increased with the amount of Tazobactam in the combination. The MICas of Cefotaxime/Tazobactam （4：1） against E. coli, K. pneumonia, A. caleoaceticus, E. cloacae, E. aerogenes, S. marcescens and C. diversus were 4, 4, 64, 32, 8, 4 and 8 μg/ml respectively, which were 4-32 folds lower than those of Cefotaxime. The antibacterial activities of Cefotaxime/Tazobactam （4：1） against E. coli and K. penumoniae were 4-8 folds higher than those of Piperacillin/Tazobactam or Cefoperazone/Sulbactam. The antibacterial activities of Cefotaxime/Tazobactam （4：1） against A. calcoaceticus, E. cloacae, E. aerogenes, S. marceseens and C. diversus were slightly higher than those of Piperacillin/Tazobactam （8：1）, lower or similar to those of Cefoperazone/Sulbactam （1：1）. Conclusion Adding of Tazobactam can effectively increase the antibacterial activities of Cefotaxime against the tested isolates except MRSA, MRSE and P. aeruginosa.