摘要
目的:探讨左氧氟沙星药代动力学/药效动力学(PK/PD)参数与金黄色葡萄球菌耐药的相关性。方法:建立兔组织笼金黄色葡萄球菌感染模型,给予不同剂量的左氧氟沙星灌胃治疗。抽取组织笼内组织液进行药代动力学测定,计算PK/PD参数,同时监测组织笼内细菌药物敏感性变化。结果:PK/PD参数AUC24/MIC、AUC24/MPC、Cmax/MIC、Cmax/MPC、T>MPC和Tmsw和耐药发生相关(MIC:最小抑菌浓度,MPC:防耐药变异浓度,MSW:耐药突变选择窗),T>MIC与耐药的发生无相关性。当AUC24/MIC在20～150h时,容易发生耐药,保持药物AUC24/MPC>25h可以限制耐药的发生。体内MSW的上、下限分别为AUC24/MPC=25h和AUC24/MIC=20h。结论:AUC24/MPC、Cmax/MPC和T>MPC可能是预测耐药发生的独立参数。
AIM：To study the correlation of levofloxacin pharmacokinetic/pharmacodynamic parameters with selection of staphylococcus aureus resistance.METHODS：Tissue cage infection model with staphylococcus aureus was established in rabbits,and the infected animals were given levofloxacin intragastrically at various doses.Changes in levofloxacin concentration,levofloxacin susceptibility of bacteria were monitored at the site of infection.RESULTS：AUC24/MIC,AUC24/MPC,Cmax/MIC,Cmax/MPC,time above MPC and Tmsw showed a statistically significant correlation with selection of staphylococcus aureus resistance,and time above MIC did not（MIC：minimal inhibitory concentration,MPC：mutant prevention concentration,MSW：mutant selection window）.Loss of bacterial susceptibility occurred easily when AUC24/MIC was between 20 h and 150 h,and keeping AUC24/MPC above 25 h could restrict selection of resistance.The upper boundary of the selection window in vivo was estimated as an AUC24/MPC value of 25 h,and the lower boundary was estimated as an AUC24/MIC value of 20 h.CONCLUSION：AUC24/MPC,Cmax/MPC and time above MPC may be the parameters for predicting resistance.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2007年第9期989-992,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金资助项目(30370615
30672505)
