细菌广谱β-内酰胺酶与超广谱酶对头孢哌酮的水解作用及两种酶抑制剂的抑酶效应  

Studies on hydrolysis of cefoperazone by broad-and extended-β-lactamaese and inhibition of β-lactamase by tazobactam and sulbactam

作　　者：张翔[1] 雷军[1] 袁斌[1] 刘刚[1] 凌保东[1] 

机构地区：[1]川北医学院药物研究所,南充637007

出　　处：《中国抗生素杂志》2006年第10期600-603,共4页Chinese Journal of Antibiotics

基　　金：四川省教育厅自然科学科研项目(No.2004A071;No.2005A081)

摘　　要：目的比较超广谱β-内酰胺酶(ESBLs)和广谱酶(BSBLs)对头孢哌酮(CPZ)的水解作用及三唑巴坦和舒巴坦之抑酶效应。方法用超声破碎法提取细菌β-内酰胺酶,用三维法鉴定β-内酰胺酶类型;用紫外分光光度计测定并计算酶活性及酶对抗生素的水解率。结果55株细菌中产超广谱酶(ESBLs)者28株,产广谱酶(BSBLs)者27株;两类酶的活性大小呈非正态分布,其中位数分别为3111.5和358U(P<0.05)。三种常见细菌的酶活性高低依次为大肠埃希菌、阴沟肠杆菌和铜绿假单胞菌(中位数分别为2218、1250和119U(P<0.05)。ESBLs对CPZ的水解率(中位数44.5%)显著高于BSBLs(中位数10.3%)(P<0.05)。TB和SB均能显著抑制两类酶对CPZ的水解作用,TB和SB对ESBLs的抑酶率>80%的比例分别为96.4%(27/28)和71.4%(20/28)(P<0.05),但两药对BSBLs的抑制效应无显著差异(P>0.05)。结论临床分离菌株的ESBLs活性高于BSBLs;ESBLs对CPZ的水解作用较BSBLs强,TB和SB能有效抑制两类酶对CPZ的水解,且TB对ESBLs的抑制作用强于SB。Objective To compare hydrolysis of cefoperazone （CPZ） by broad-spectrum β-lactamaese （BSBLs） with that by extended-spectrum β-lactamaese（ESBLs） and detect inhibiting-β-lactamaese activities of tazobactam （TB） and sulbactam （SB）. Methods Fifty five strains of Gram-negative bacilli from the Affiliated Hospital of North Sichuan Medical College （Nanchong City, Sichuan Province） were disrupted with ultrasonic wave and their β-1actamases were extracted. Three dimensional test for β-lactamase was performed. β-Lactamase activities, hydrolysis rate （HR） of CPZ and inhibiting-β-lactamase rate （IR） of SB and TB was quantitated spectrophotometrically and calculated. Results In these β-lactamases producers, the ESBLs- and BSBLs-producing organisms were 28 and 27, respectively. The medians of ESBLs and BSBLs activities were 3094U and 528U, respectively （P〈0. 05）. The median ezyme activities of Escherichia coli, Enterobacter cloacae and Pseudomonas aeruginosa were 2656U, 1185U and 165.5U, respectively （ P 〈0.05）. The medians of CPZ HR by ESBLs and BSBLs were 44.5% and 10. 3%, respectively （P〈0.05）. The combination of CPZ/TB and CPZ/SB （2： 1） could make the HR drop significantly （ P〈0. 05）. Among 28 ESBLs producers, the ＂IR〉80% ＂strains by TB and SB were 27 and 20, respectively （ P〈0. 05）. Conclusion The hydrolysis activities of ESBLs on CPZ was higher than those of BSBLs. TB and SB could effectively inhibit hydrolysis of CPZ by ESBLs and BSBLs, and the ability of TB in preventing hydrolysis of CPZ by ESBLs was more potent than SB.

关 键 词：头孢哌酮 三唑巴坦 舒巴坦 超广谱β 内酰胺酶 细菌 水解 

分 类 号：R978.11[医药卫生—药品]