几种抗菌药物在不同浓度时对金黄色葡萄球菌耐药突变株选择的影响

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (2): 163-167.

几种抗菌药物在不同浓度时对金黄色葡萄球菌耐药突变株选择的影响

李朝霞¹, 刘又宁¹, 王睿², 童卫杭², 程仕虎¹

¹解放军总医院呼吸内科, ²临床药理研究室, 北京 100853

收稿日期:2006-09-13 修回日期:2006-10-27 出版日期:2007-02-26 发布日期:2020-10-27
通讯作者: 刘又宁, 通讯作者, 男, 医学博士, 教授, 博士生导师, 研究方向:肺部感染性疾病和呼吸衰竭的诊断治疗。Tel:010-66939366 E-mail:liuyn@301hospital.com.cn
作者简介:李朝霞, 女, 博士研究生, 主治医师, 研究方向:肺部感染性疾病和细菌耐药机制研究。Tel:010-66937187 　E-mail:lzx99@vip.sinacom

Studies on effect of drug concentration on selection of resistant mutants of staphylococcus aureus

LI Zhao-xia¹, LIU You-ning¹, WANG Rui², TONG Wei-hang¹, CHENG Shi-hu¹

¹Department of Respiratory, ²Department of Clinical Pharmacology, General Hospital of PLA, Beijing 100853, China

Received:2006-09-13 Revised:2006-10-27 Online:2007-02-26 Published:2020-10-27

摘要/Abstract

摘要： 目的: 了解左氧氟沙星、万古霉素、利福平、氯霉素、妥布霉素、阿齐霉素在不同浓度时对金黄色葡萄球菌ATCC29213 耐药突变株选择的影响。将它们对金黄色葡萄球菌的最低抑菌浓度(MIC) 、防耐药变异浓度(MPC) 、突变选择窗(MSW) 与药代动力学参数结合, 为制定新的抗菌药物用药策略提供依据。方法: 应用肉汤富集细菌法测定左氧氟沙星、万古霉素、利福平、氯霉素、妥布霉素、阿齐霉素对金黄色葡萄球菌ATCC29213 的防MPC;琼脂平板二倍稀释法测定MIC;将金黄色葡萄球菌ATCC29213 接种于不同药物浓度的琼脂平板上, 计数平板上恢复生长的菌落数, 描记细菌恢复生长曲线。结果: 左氧氟沙星、万古霉素、利福平、阿奇霉素、氯霉素和妥布霉素对金黄色葡萄球菌ATCC29213 的MIC 分别为0.125 、1.0 、0.002 、0.5 、3.0 、0.5 μg/mL;MPC 分别为1.4 、51.2 、>1024 、4.8 、16 、16 μg/mL;6 种抗菌药物-金黄色葡萄球菌ATCC29213 组合的MSW 差异很大, 以利福平的MSW 最宽(SI:>512 000), 氯霉素的MSW 最窄(SI:5.3) 。不同抗菌药物-金黄色葡萄球菌的菌落恢复生长曲线各不相同。结论: 药物浓度对金黄色葡萄球菌恢复生长的耐药突变株菌落数有明显影响。在临床上, 可以通过将MPC 结合药代动力学参数, 来选择药物浓度和用药方式, 从而达到减少细菌耐药的目的。

关键词: 细菌恢复生长曲线, 防耐药变异浓度, 金黄色葡萄球菌, 耐药

Abstract: AIM: To study the effect of levofloxacin, vancomycin, rifampin, azithromycin, tobramycin and chloramphenicol concentration on selection of resistant mutants of staphylococcus aureus ATCC29213.Also to combine minimal inhibitory concentration (MIC), mutant prevention concentration (MPC) and mutant selection window (MSW) with pharmacokinetic parameters and then provide evidence for new strategies for restricting the development of resistance.METHODS: The agar dilution method was carried out on drug-containing agar according to NCCLS guidelines to determine MIC of levofloxacin, vancomycin, rifampin, azithromycin, tobramycin and chloramphenicol against ATCC29213.MPC was determined by the agar dilution according to MIC determining except that ATCC29213 were enriched in broth, and the bacterial concentrations were adjusted to 1010 colony form units per milliliter.Staphylococcus aureus were plated on agar containing various antimicrobial concentrations.The fraction of bacteria recovered curve was traced by colony counting.RESULTS: The MPCs of levofloxacin, vancomycin, rifampin, azithromycin, tobramycin and chloramphenicol for staphylococcus aureus strain ATCC29213 were 1.4, 51.2,>1024, 4.8, 16, and 16 μg/mL;the MICs of them were 0.125, 1.0, 0.002, 0.5, 3.0, and 0.5μg/mL respectively;and the MSW of each antimicrobialstaphylococcus aureus combination was distinct.The MSW of rifampin-staphylococcus aureus was the broadest, and the MSW of chloramphenicol-staphylococcus aureus was the narrowest.The fraction of bacteria recovered curve varied considerably among the bacterium-antimicrobial combinations.CONCLUSION: Antimicrobial concentrations have strong effect on the recovery and selection of resistant colonies.In clinical practice, the selection of resistant mutants could be prevented by choosing antimicrobial concentration and medication in combining MPC with pharmacokinetic parameters.

Key words: fraction of bacteria recovered curve, mutant prevention concentration, staphylococcus aureus, drug resistant

中图分类号:

R965.1

李朝霞, 刘又宁, 王睿, 童卫杭, 程仕虎. 几种抗菌药物在不同浓度时对金黄色葡萄球菌耐药突变株选择的影响[J]. 中国临床药理学与治疗学, 2007, 12(2): 163-167.

LI Zhao-xia, LIU You-ning, WANG Rui, TONG Wei-hang, CHENG Shi-hu. Studies on effect of drug concentration on selection of resistant mutants of staphylococcus aureus[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(2): 163-167.

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