氟喹诺酮类药物对金黄色葡萄球菌及其耐药突变体的耐药性研究

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (6): 696-701.

氟喹诺酮类药物对金黄色葡萄球菌及其耐药突变体的耐药性研究

李朝霞, 刘又宁, 王睿¹, 崔俊昌, 程仕虎, 童卫杭¹

解放军总医院呼吸内科, ¹临床药理研究室, 北京 100853

收稿日期:2006-01-13 修回日期:2006-03-28 出版日期:2006-06-26 发布日期:2020-12-04
通讯作者: 刘又宁,男,教授,医学博士,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,主治医师,博士研究生,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

In vitro studies of mutant prevention concentration and mutant selective window for staphylococcus aureus and its isogenic mutants strain

LI Zhao-xia¹, LIU You-ning, WANG Rui¹, CUI Jun-chang, CHENG Shi-hu, TONG Wei-hang

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

Received:2006-01-13 Revised:2006-03-28 Online:2006-06-26 Published:2020-12-04

摘要/Abstract

摘要： 目的: 研究5 种氟喹诺酮类药物(FQ) 对金黄色葡萄球菌ATCC29213 及其同源耐药突变体的最低抑菌浓度(MIC)、防细菌耐药突变体选择浓度(MPC) 和突变选择窗(MSW), 比较其防耐药变异能力, 了解细菌对FQ 耐药的发生发展过程。方法: 肉汤法富集1010 CFU·ml^-1 金黄色葡萄球菌ATCC29213, 采用平板稀释法测定莫西沙星、加替沙星、司帕沙星、左氧氟沙星和环丙沙星对金黄色葡萄球菌ATCC29213 及筛选的耐药突变体的MIC、暂定MPC(MPCpr) 和MPC。结果: 莫西沙星、加替沙星、司帕沙星、左氧氟沙星和环丙沙星对金黄色葡萄球菌ATCC29213 的MPC 分别为0.2、0.3、0.3、1.4、3.2 μg·ml^-1。选择指数(MPC MIC) 分别为6.5、4.8、9.7、11.2、12.8。5 种氟喹诺酮类药物筛选的第一步突变体对筛选药物的MIC 较ATCC29213 升高2~8倍。左氧氟沙星筛选的第二步突变体的MIC 较第一步突变体又升高8~16 倍。所有突变体的MSW边界都较其源菌株明显升高。结论: 莫西沙星、加替沙星限制金黄色葡萄球菌耐药突变菌体选择的能力强于司帕沙星、左氧氟沙星和环丙沙星。金黄色葡萄球菌对FQ 药物产生耐药是逐步发生的。第一步耐药突变体的产生, 使筛选出下一步耐药突变体的几率明显增大, 从而导致耐药菌的富集和扩散。

关键词: 防细菌耐药突变体选择浓度, 突变选择窗, 氟喹诺酮类, 金黄色葡萄球菌

Abstract: AIM: To measure minimal inhibitory concentration (MIC), mutant prevention concentration (MPC) and mutant selection window (MSW) of fluoroquinolones for staphylococcus aureus strain ATCC29213, and isogenic mutants of strain ATCC29213 in vitro,MSW and the capacity of fluoroquinolones for restricting the selection of next-step staphylococcus aureus resistant mutants were evaluated.In the meantime, the emergence and development of fluoroquinolones resistant were observed.Methods: The celles of 1010 colony form units per milliliter staphylococcus aureus were enriched in broth, and theMIC, provisional MPC (MPCpr) and MPC of fluoroquinolones against different strains were determined by agar plates dilution method.Results: The MPCs of moxifloxacin, gatifloxacin, Sparfloxacin, levofloxacin and Ciprofloxacin for staphylococcus aureus strain ATCC29213 were 0.2, 0.3, 0.3, 1.4, 3.2 μg·ml^-1, and the MPC MICs were 6.5, 4.8, 9.7, 11.2 and 12.8 respectively. The MICs of 5 fluoroquinolones for the first-step isogenic mutants were 2-8 folds greater than those of ATCC29213.The MICs of levofloxacin for the secondstep mutants were 8-16 folds greater than those of the first-step isogenic mutants.The MSWs of 5 fluoroquinolones for the mutants were wider than those for its isogenic strain.Conclusion: For staphylococcus aureus strain ATCC29213 and its isogenic mutants, the capacity of moxifloxacin and gatifloxacin for restricting the selection of next-step resistant mutants is stronger than that of sparfloxacin, levofloxacin and ciprofloxacin.The staphylococcus aureus resistance of fluoroquinolones is developed step by step.The emergence of the first-step mutants is more easily to select new mutants.

Key words: mutant prevention concentration, mutant selection window, fluoroquinolones, staphylococcus aureus

中图分类号:

R965

李朝霞, 刘又宁, 王睿, 崔俊昌, 程仕虎, 童卫杭. 氟喹诺酮类药物对金黄色葡萄球菌及其耐药突变体的耐药性研究[J]. 中国临床药理学与治疗学, 2006, 11(6): 696-701.

LI Zhao-xia, LIU You-ning, WANG Rui, CUI Jun-chang, CHENG Shi-hu, TONG Wei-hang. In vitro studies of mutant prevention concentration and mutant selective window for staphylococcus aureus and its isogenic mutants strain[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(6): 696-701.

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