氨苄西林的体外抗菌后效应及抗菌后亚抑菌浓度效应研究

Postantibiotic effect and postantibiotic sub-MIC effect of ampicillin

采用菌落计数法测定了氨苄西林对4株细菌的体外抗菌后效应(PAE),以及对2株细菌的体外抗菌后亚抑菌浓度效应(PASME)。结果显示,氨苄西林在0.5,1,2,4×MIC浓度时,对金黄色葡萄球菌C26112的PAE值分别为1.14±3.05,1.62±2.11,1.87±1.70和2.45±1.31h,对金黄色葡萄球菌临床分离株的PAE值分别为1.05±1.84,1.38±1.25,1.56±1.35和2.29±2.04h;对大肠杆菌ATCC25922和临床分离株的PAE很小甚至没有;在1/8,1/4,1/2×MIC时对金黄色葡萄球菌C26112及临床分离株的PASME值分别为3.61±1.38,4.75±2.18,6.8±1.51h和3.01±2.5,4.2±1.21,5.9±1.23h;氨苄西林对金黄色葡萄球菌的PAE(0.5～4×MIC)及PASME(1/8～1/2MIC)与浓度在一定范围内呈剂量依赖性,并且在亚抑菌浓度下也具有PAE,当药物浓度达4×MIC时,PAE明显延长(P<0.05),且所测得的PASME较PAE长。所有结果提示:在临床设计给药方案时,对金黄色葡萄球菌敏感株引起的临床感染,除了考虑药代动力学和MIC指标外,还应考虑PAE和PASME因素,可适当延长给药间隔时间;而对PAE无意义的大肠杆菌敏感株引起的临床感染,宜持续给药或缩短给药间隔,也可达到较好的治疗效果。

This study was designed to investigate the postantibiotic effect (PAE) of ampicillin on Staphylococcus aureu and Escherichia coli in vitro and postantibiotic sub-MIC effect on staphylococcus aureu.The dilution method was used for the drug removal and Muelle-Hinton agar colony counting method was used to monitor the growth of bacteria.The results showed that marked PAEs were found even in the subinhibitory concentration (sub-MIC) when ampicillin was used against S.aureus C_( 26112) and S.aureu obtained from veterinary clinic,and PAEs was 1.14±3.05,1.62±2.11,1.87±1.70,2.45±1.31 h and ( 1.05±)1.84,1.38±1.25,1.56±1.35,2.29±2.04 h,respectively.When S.aureus was exposed to ampicillin for 1 h,the PASMEs could be got after successively exposing to 1/8,1/4,1/2×MIC ampicillin and the values were 3.61±1.38,4.75±2.18,6.8±1.51 h (for S.aureu C_( 26112)) and 3.01±2.5,4.2±1.21,( 5.9±)( 1.23 h) (for S.aureu from veterinary clinic).The duration of PAEs and PASMEs was enhanced with increasing concentration,showing strongly a concentration-dependent dependance,especially at 4×MIC,the PAE was obviously prolonged (P<0.05).Negative PAEs were defined,however,when the drug was used against E.coli at the same concentration.Taken together,our data indicate that the phenomenon of PAE and PASME may help in the design of efficient control strategies for some infections in animals,for example,longer dosing interval should be recommended when the two drugs are against S.aureu,however,successive dosing or shorted dosing interval should be taken when they are used against sensitive E.coli.