2种氟喹诺酮类药物对临床分离金黄色葡萄球菌突变选择窗的影响

目的通过测定左氧氟沙星及莫西沙星对金黄色葡萄球菌临床分离菌株防突变浓度(MPC),比较氟喹诺酮类对金黄色葡萄球菌突变选择窗(MSW)的影响,为临床合理使用抗菌药物,防治细菌耐药产生提供依据。方法采用标准琼脂二倍稀释法测定2种氟喹诺酮药物对38株临床分离的金黄色葡萄球菌和金黄色葡萄球菌质控菌株ATCC25923的最低抑菌浓度(MIC),采用肉汤法富集3×1010CFU.mL-1的金黄色葡萄球菌测定2种氟喹诺酮药物MPC,计算MPC50、MPC90、MPC/MIC。结果左氧氟沙星对38株金黄色葡萄球菌的MPC90、MPC90/MIC90分别为16 mg.L-1、8,莫西沙星分别为2 mg.L-1、4;结合药物动力学参数莫西沙星400 mg.次-1,1次.d-1,其Cmax/MPC90、AUC/MPC90分别为2.3、18,左氧氟沙星500 mg.次-1的Cmax/MPC90、AUC/MPC90明显高于300 mg.d-1组,分别为0.5、2.4。结论对金黄色葡萄球菌的临床分离菌株莫西沙星比左氧氟沙星MPC90低,MSW窄,防突变能力更强。左氧氟沙星500 mg.次-1,1次.d-1,能够提高左氧氟沙星的防突变能力。

Effect of single and combination of fluoroquinolones in vitro on mutant selection window of staphylococcus aureus

Objective To determine the mutant prevention concentration（MPC）of 2 fluoroquinolones on staphylococcus aureus isolates,compare MPC and MPC/MIC（selective index,SI）,and study the effect of the drug combination on the mutant selection window（MSW） in vitro.Methods The MIC for staphylococcus aureus isolates and quality control（ATCC25923） were determined by the standard 2 fold agar dilution method.The cells of 3×1010colony forming units per milliliter staphylococcus were enriched in broth.The MPC of fluoroquinolones against the strains were determined by agar dilution method.The value of MIC50,MIC90,MPC50,MPC90 and MPC/MIC was calculated.SPSS was used to analyze the data.Results The MPC90 and MPC90/MIC90 of levofloxacin were 16 mg·L-1 and 8.Moxifloxacin had lower MPC90 and MPC90/MIC90（2 mg·L-1 and 4 respectively）.The Cmax/MPC90 and AUC/MPC90 values were 2.3 and 18.The Cmax/MPC90 and AUC/MPC90 values of levofloxacin 500 mg once daily were 0.5 and 2.4,higher than 300 mg once daily.Conclusion Moxifloxacin exhibits lower MPC,narrower MSW and better ability of resistant mutants than levofloxacin.The regimen like levofloxacin 500 mg once daily has advantage in resistance mutation prevention.