仿制和原研左氧氟沙星的体外抗菌活性比较

Evaluation of in vitro antibacterial activity of both generic and brand-name levofloxacin

目的比较仿制和原研左氧氟沙星的体外抗菌活性,为临床抗菌药物生物等效性评价提供参考。方法收集本院常见临床菌株共154株,其中金黄色葡萄球菌48株,铜绿假单胞菌52株,大肠埃希菌54株,根据美国临床和实验室标准协会(CLSI)推荐的琼脂二倍稀释法进行抗菌药物敏感性试验。结果仿制和原研左氧氟沙星对所有质控菌株的体外抗菌活性相似,MIC值相差不超过±1个稀释梯度;但对于临床菌株,原研药体现出更强的抑制作用,尤其是在低药物浓度下差异更加明显,且个别仿制药与其对比存在MIC值相差4倍的情况。结论市售各厂牌左氧氟沙星仿制药对临床重要致病菌的体外抗菌活性较原研药存在一定差异,建议在对抗菌药物进行仿制药一致性评价时应结合其PK/PD特性,进行相应的技术细化,引入基于各MIC值水平下的累积抑菌百分率进行对比,确保仿制药在真实的临床细菌耐药情况下与原研药具有相同的抗菌活性。

Objective To evaluate the in vitro antibacterial activity of levofloxacin for both brand-name and generic manufactured drugs,and to provide a reference for the evaluation of the clinical bioequivalence of antibacterial drugs.Methods A total of 154 common clinical strains were collected in-house,including 48 strains of Staphylococcus aureus,52 strains of Pseudomonas aeruginosa,and 54 strains of Escherichia coli,according to agar doubling dilution method recommended by the American Association of Clinical and Laboratory Standards.The doubling dilution method was used for antimicrobial susceptibility test.Results The minimum inhibitory concentration (MIC) values of levofloxacin for both generic and brand-name drugs did not exceed±1 dilution gradient for all quality control strains,however for clinical strains,the brand-name drug showed stronger inhibition especially at low drug concentration,and the difference was more obvious.Moreover the MIC value differed by 4 times.Conclusion The levofloxacin generic drugs in the market have different in vitro antibacterial activities against clinically important pathogenic bacteria than the brand-name drugs.It is recommended that the antimicrobial drug consistency evaluation should be combined with the PK/PD characteristics.The accumulative inhibition percentage at different minimum inhibitory concentrations are critical and thus must be provided to ensure that the generic drugs have the same antibacterial activity as the brand-name drugs under the actual clinical bacterial resistance.