注射用头孢拉宗钠的体内外抗菌活性研究

In vitro and in vivo antibacterial activity of cefbuperazone sodium

目的评价注射用头孢拉宗钠的体内外抗菌活性。方法选取663株临床分离致病菌为实验菌,以头孢美唑、头孢西丁、头孢替坦、头孢米诺、头孢唑啉、头孢呋辛、头孢哌酮、头孢吡肟为对照药物,分别采用平皿二倍稀释法测定药物最低抑菌浓度(MIC)、最低杀菌浓度(MBC)、绘制杀菌曲线(KCs)并行诱导耐药实验,观察头孢拉宗的体外抗菌作用;建立小鼠腹腔感染模型,评价头孢拉宗皮下给药对金黄色葡萄球菌、大肠埃希菌、肺炎克雷伯杆菌感染小鼠的体内疗效。结果头孢拉宗对多种革兰阴性菌具有较高的抗菌活性,尤以对大肠埃希菌和肺炎克雷伯杆菌的抗菌活性更为突出,其MIC50、MIC90分别为0.5、8μg/ml,对产超广谱β-内酰胺酶大肠埃希菌和肺炎克雷伯杆菌的抗菌活性也较强,其MIC50、MIC90分别为4、8μg/ml;头孢拉宗对革兰阴性菌的抗菌作用大多优于头孢西丁、头孢美唑、头孢唑啉、头孢哌酮、头孢替坦和头孢呋辛,而对革兰阳性菌的抗菌活性较弱,与头孢替坦和头孢米诺相近。MBC和KCs测定结果表明,头孢拉宗对金黄色葡萄球菌、大肠埃希菌、肺炎克雷伯杆菌均具有杀菌作用。以1/4MIC剂量诱导20d后,头孢拉宗对金黄色葡萄球菌、大肠埃希菌和肺炎克雷伯杆菌的抗菌活性无明显改变。头孢拉宗皮下给药对大肠埃希菌ATCC25922、大肠埃希菌1515、肺炎克雷伯杆菌7、肺炎克雷伯杆菌9613感染小鼠的体内疗效明显优于头孢美唑和头孢唑啉(均P<0.01);对金黄色葡萄球菌感染小鼠的体内疗效与头孢美唑相近(P>0.05),但弱于头孢唑啉(P<0.01)。结论注射用头孢拉宗钠对多数革兰阴性菌,特别是大肠埃希菌和肺炎克雷伯杆菌具有较强的体外抗菌活性;同时对大肠埃希菌、肺炎克雷伯杆菌、金黄色葡萄球菌腹腔感染小鼠的体内疗效也较好。

Objective To investigate the in vitro and in vivo antibacterial activity of cefbuperazone.Methods The 663 clinical isolated bacteria were selected for experiment,and cefmetazole,cefoxitin,cefotetan,cefminox,cefazolin,cefuroxime,cefoperazone,cefepime were used for control drugs.The minimal inhibitory concentrations （MIC） were determined by agar dilution method,detecting the MBC,KCs and performing induced resistance experiment,in order to observe the in vitro antibacterial activity of cefbuperazone.The E.coli,K.pneumoniae and S.aureus.were intraperitoneally infected in mice to establish infection model,and evaluating the in vivo antibacterial activities of cefbuperazone by subcutaneous administration.Results Cefbuperazone showed strong antibacterial activity against most of the gram-negative bacteria.The MIC50s and MIC90s of cefbuperazone were 0.5,8 μg/ml against Escherichia coli and Klebsiella pneumoniae,4,8 μg/ml against β-lactamases-producing E.coli and K.pneumoniae.The antibacterial activities of cefbuperazone against most of the gram-negative bacteria were more potent than cefoxitin,cefmetazole,cefazolin,cefoperazone,cefotetan,and cefuroxime,but the antibacterial activities of cefbuperazone against gram-positive bacteria were weak,similar to cefotetan and cefminox.MBC and KCs showed that cefbuperazone was bactericidal against E.coli,K.pneumoniae and S.aureus.After inducing with 1/4 MIC dose for 20 d in vitro,the induction of resistance to cefbuperazone showed no effect on antibacterial activities against S.aureus,E.coli and K.pneumoniae.Cefbuperazone given by subcutaneous was effective on mice systemically infected with E.col ATCC25922,E.col 1515,K.pneumoniae 7 and K.pneumoniae 9613,the in vivo activity was higher than cefmetazole and cefazolin （all P 0.01）.Cefbuperazone given by subcutaneous had similar effects to cefmetazole on mice systemically infected with S.aureus （P 0.05）,but weaker than cefazolin （P 0.01）.Conclusions Cefbuperazone has excellent in vitro antibacterial activities against most of the gram-negative bacteria especially E.coli and K.pneumoniae.Cefbuperazone has relatively good protection to mice with systemic infections caused by E.coli,K.pneumoniae and S.aureus.