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  

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

作　　者：李朝霞[1] 刘又宁[1] 王睿[2] 崔俊昌[1] 程仕虎[1] 童卫杭[2] 

机构地区：[1]解放军总医院呼吸内科,北京100853 [2]解放军总医院临床药理研究室,北京100853

出　　处：《中国临床药理学与治疗学》2006年第6期696-701,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

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10^10CFU·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ATC29213的MPC分别为0．2、0．3、0．3、1．4、3．2μg·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。AIM： To measure minimal inhibitory concentration （ MIC ）, mutant prevention concentration （MPC） and mutant selection window （MSW） of fluoro- quinolones 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 10^10 colony form units per milliliter staphylococcus aureus were enriched in broth, and the MIC, 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, 3.2μg· 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 second-step 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 spar-floxacin, 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.

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 

分 类 号：R965[医药卫生—药理学]