左氧氟沙星药代动力学/药效动力学参数与金黄色葡萄球菌耐药的相关性研究

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (9): 989-992.

左氧氟沙星药代动力学/药效动力学参数与金黄色葡萄球菌耐药的相关性研究

崔俊昌¹, 刘又宁¹, 王睿², 童卫杭², 梁蓓蓓²

¹解放军总医院呼吸科, ²临床药理研究室, 北京100853

收稿日期:2007-06-05 修回日期:2007-08-31 出版日期:2007-09-26 发布日期:2020-10-30
通讯作者: 刘又宁, 男, 教授, 博士生导师, 研究方向:细菌耐药性。Tel:010-66939366 E-mail:liuyn@301hospital.com.cn
作者简介:崔俊昌, 男, 博士, 副主任医师, 研究方向:细菌耐药性。Tel:010-66939360 E-mail:cuijunchang@163.com
基金资助:
国家自然科学基金资助项目(30370615;30672505)

Correlation of levofloxacin pharmacokinetic/pharmacodynamic parameters with selection of staphylococcus aureus resistance

CUI Jun-chang¹, LIU You-ning¹, WANG Rui², TONG Wei-hang², LIANG Bei-bei²

¹Department of Respiratory Diseases, ²Department of Clinical Parmacology, Chinese People's Liberation Army General Hospital, Beijing 100853, China

Received:2007-06-05 Revised:2007-08-31 Online:2007-09-26 Published:2020-10-30

摘要/Abstract

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、C_max/MIC、C_max/MPC、T >MPC 和T_msw 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AUC24MIC 在20～150 h 时, 容易发生耐药, 保持药物AUC₂₄/MPC >25 h 可以限制耐药的发生。体内MSW 的上、下限分别为AUC₂₄/MPC=25 h 和AUC24MIC=20 h。结论:AUC₂₄/MPC、C_max/MPC 和T >MPC 可能是预测耐药发生的独立参数。

关键词: 左氧氟沙星, 药代动力学/药效动力学, 金黄色葡萄球菌, 耐药突变选择窗

Abstract: 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, C_max/MIC, C_max/MPC, time above MPC and T_msw 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, C_max/MPC and time above MPC may be the parameters for predicting resistance.

Key words: levofloxacin, pharmacokinetic/pharmacodynamic, staphylococcus aureus, mutant selection window

中图分类号:

崔俊昌, 刘又宁, 王睿, 童卫杭, 梁蓓蓓. 左氧氟沙星药代动力学/药效动力学参数与金黄色葡萄球菌耐药的相关性研究[J]. 中国临床药理学与治疗学, 2007, 12(9): 989-992.

CUI Jun-chang, LIU You-ning, WANG Rui, TONG Wei-hang, LIANG Bei-bei. Correlation of levofloxacin pharmacokinetic/pharmacodynamic parameters with selection of staphylococcus aureus resistance[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(9): 989-992.

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