利他唑酮干混悬剂体内抗菌作用研究  

In vivo antibacterial activity of litazolid dry suspension

作　　者：朱珍真[1] 陈贞[1] 郎丽巍[1] 王红艳[1] 李岳 王琪 魏振满[1] 鲁韬 

机构地区：[1]解放军第三〇二医院药学部药物临床试验中心,北京100039 [2]四川赛卓药业股份有限公司,绵阳621000

出　　处：《中国抗生素杂志》2018年第2期249-254,共6页Chinese Journal of Antibiotics

基　　金：国家十二五重大新药创制;国家重大科技专项课题(No.2014ZX09201001-008)

摘　　要：目的研究利他唑酮(LT-01)干混悬剂对败血症和急性肺炎小鼠的体内抗菌作用。方法以耐万古霉素屎肠球菌(vanomycin-resistant enterococci,VRE)感染败血症和耐甲氧西林金黄色葡萄球菌(methicillin resistant Staphylococcus aureus,MRSA)/青霉素不敏感的肺炎链球菌(penicillin nonsusceptible Streptococcus pneumoniae,PNSSP)感染急性肺炎小鼠为动物模型,灌胃给与LT-01干混悬剂及利奈唑胺片,比较两药对感染小鼠的保护作用,以及对肺炎小鼠肺部活菌清除作用。结果 LT-01干混悬剂对VRE感染小鼠败血症模型以及MRSA感染小鼠急性肺炎模型的ED_(50)分别为4.441和9.550mg/kg,略优于市售利奈唑胺片(ED_(50)分别为6.656和13.843mg/kg);对亚致死量的MRSA和PNSSP感染小鼠急性肺炎模型的24h肺部活菌清除效果与利奈唑胺片相似或略低,但48h的细菌清除效果优于利奈唑胺。结论实验结果表明LT-01干混悬剂对革兰阳性球菌有很好的抗菌作用,提示LT-01是一种可用于临床治疗耐药革兰阳性球菌感染的药物,值得进一步开发研究。Objective To study the antibacterial effect in vivo of litazolid （LT-01） dry suspension in models of systemic infections and acute pneumonia. Methods We set up a systemic infection model caused by vanomycin- resistant enterococci （VRE） and pneumonia models produced by intranasal inoculation of methicillin resistant Staphylococcus aureus （MRSA） and penicillin nonsusceptible Streptococcus pneumoniae （PNSSP）. Both litazolid and linezolid were administered orally. After the administration, we compared the survival number of mice among each group, and we also compared the bacterial clearance in the lungs among each group. Results In the systemic infection model caused by VRE and pneumonia models produced by MRSA, the 50% effective doses （ED50） of LT-01 were 4.441 and 9.550mg/kg, which were slightly better than linezolid （the EDs0 of linezolid were 6.656 and 13.843mg/kg）. In acute pneumonia models caused by sub lethal dose of MRSA/PNSSP, the bacterial clearance effects of LT-01 in the lungs was similar to or slightly lower than linezolid at 24h after administration. At 48h, however, the clearance effects of LTo01 was better than that of linezolid. Conclusion The experimental results showed that LT-01 had a good antibacterial effect on Gram-positive bacteria, suggesting that LT-01 was a new drug that can be used in the clinical treatment of infections caused by drug resistant Gram-positive bacteria, which was worthy of further research.

关 键 词：利他唑酮 利奈唑胺 急性肺炎模型 败血症模型 耐药革兰阳性球菌 

分 类 号：R978.1[医药卫生—药品]