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  

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

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

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》2007年第2期163-167,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

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、0.5μg/mL;MPC分别为1.4、51.2、>1024、4.8、16、16μg/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:>512000),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。AIM： To vancomycin, rifampin, study the effect of levofloxacin, azithromycin, tobramycin and ehloramphenicol 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 pharmaeokinetie parameters and then provide evidence fi）r 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 levofloxaein, vaneomycin, rifampin, azithromyein, tobramycin and chloeamphenieol 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 10^10 colony form units per milliliter. Staphlococcus aureus were plated on agar containing various antimierobial 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 0.5 μ/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 crave 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 antimi- crobial concentration and medication in combining MPC with pharmacokinetic parameters.

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 

分 类 号：R965.1[医药卫生—药理学]