细菌广谱酶与超广谱酶对头孢噻肟的水解作用及酶抑制剂抑酶效应  

Studies on hydrolysis of cefotaxime by broad and extended-spectrum-β-lactamase and inhibitory actions of tazobactam and sulbactam

作　　者：张翔[1] 雷军[1] 袁斌[1] 刘刚[1] 赵廷坤[1] 凌保东[1] 

机构地区：[1]川北医学院药物研究所,四川南充637007

出　　处：《药学实践杂志》2007年第6期376-378,共3页Journal of Pharmaceutical Practice

基　　金：四川省教育厅自然科学重点科研项目(No.2005A081)

摘　　要：目的:观察比较头孢噻肟(CTX)对细菌广谱及超广谱β-内酰胺酶的稳定性以及三唑巴坦(TAZ)和舒巴坦(SBT)的抑酶效应。方法:用超声破碎法提取60株本院附属医院临床分离菌的β-内酰胺酶,用三维试验法检测β-内酰胺酶酶型;用紫外分光光度计检测酶活性及酶对CTX的水解率。结果:60株细菌中产超广谱酶者31株,产广谱酶者29株;两类酶的活性为非正态分布,其中位数分别为3 094 U和528 U(P<0.05)。3种常见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孢菌(中位数分别为2656 U,1185 U和165.5 U,P<0.05)。超广谱酶对CTX的水解率(中位数20.10%)显著高于广谱酶(中位数3.15%)(P<0.05)。TAZ和SBT均能显著抑制两类酶对CTX的水解作用,但两种酶抑制剂的作用无差异(P>0.05)。结论:超广谱酶(ESBLs)对CTX的水解作用较广谱酶强,TAZ和SBT能有效抑制两类酶对CTX的水解,但其抑制作用强度基本相同。Objective：To observe the stability of cefotaxime （CTX） to broad-and extended-spectrum β-lactamase, and to compare in- hibiting-β-lactamase activities of tazobactam and sulbactam. Methods： 60 strains of Gram-negative bacilli from Affiliated Hospital of North Sichuan Medical College were dealed with ultrasonic wave and their β-lactamases were extracted and these enzymes were detected by three-dimensional test. β-lactamase activitiy and hydrolysis of CTX were quantitated spectrophotometrically and calculated. Results ： In these β-lactamases of 60 strains of Gram-negitive bacilli, the number of extended-spectrum β-lactamases and broad-spectrum β-lactamases were 31 and 29, respectively, and their medians of enzyme activities were 3 094 U and 528 U （P 〈 0.05 ）. The medians of β-lactamases activities of Escherichia coli ,Enterobacter cloacae and Pseudomonas aeruginosa were 2 656 U, 1 185 U and 165.5 U, respectively. The median of hydrolysis rates （HR） of CTX by ESBLs and BSBLs were 20.10% and 3.15%, respectively（P 〈0.05）. The combination of CTX/TAZ and CTX/SBT （the ratio = 2 ： 1 ） could make the HR drop significantly （P 〈 0.05）, but the effects of TAZ and SBT were of no differences （P 〉 0.05）. Conclusion：The hydrolysis activities of ESBLs on CTX was higher than that of BSBLs. TAZ and SBT could effectively inhibit hydrolysis of CTX by β-lactamases, but these two inhibitors had little difference in their potency.

关 键 词：头孢噻肟 三唑巴坦 舒巴坦 超广谱β-内酰胺酶 广谱酶 革兰阴性杆菌 水解 

分 类 号：R977.3[医药卫生—药品]