利他唑酮体外抗菌活性研究  

In vitro antimicrobial activity of litazolid

作　　者：曲芬[1] 张鞠玲[1] 王欢[1] 张成龙[1] 贾田野 袁媛[1] 庞君丽[1] 张树永[1] 陈素明[1] 鲍春梅[1] 李岳 鲁韬 王琪[3] Qu Fen Zhang Ju-ling Wang Huan Zhang Cheng-long Jia Tian-ye Yuan Yuan Pang Jun-li Zhang Shu-yong Chen Su-ming Bao Chun-mei Li Yue Lu Tao Wang Qi(Clinical Laboratory Center, 302 Hospital ofPLA, Beijing 100039 Sichuan Saizhuo Pharmaceutical Corporation Limited, Chengdu 610063 Peking University Institute of Clinical Pharmacology Beijing 100034)

机构地区：[1]解放军302医院,北京100039 [2]四川赛卓药业股份有限公司,成都610063 [3]北京大学临床药理研究所,北京100034

出　　处：《中国抗生素杂志》2016年第12期942-949,共8页Chinese Journal of Antibiotics

基　　金："重大新药创制"国家十二五科技重大专项课题(No.2014ZX09201001)

摘　　要：目的评价利他唑酮（LT-01）对临床分离致病菌的体外抗菌活性，并考察细菌接种量、培养基pH值、血清含量对抗菌作用的影响，同时研究LT-01的主要代谢产物M1对革兰阳性球菌的体外抗菌活性。方法对来自解放军302医院的859株临床分离致病菌进行了MICN定。最低抑菌浓度fMICl测定采用琼脂二倍稀释法：最低杀菌浓度（MBC）测定采用肉汤二倍稀释法；杀菌曲线绘制采用菌落计数法。结果LT-01对革兰阳性菌，包括耐甲氧西林金黄色葡萄球菌（MRSA）、耐甲氧西林表皮葡萄球菌（MRSE）、青霉素不敏感肺炎链球菌（PNSSP）、耐万古霉素肠球菌（VRE）等耐药菌株具有较好抗菌活性，与利奈唑胺相仿，对于多数革兰阴性菌基本无效。各影响因素实验结果显示，LT-01的MIC值随着细菌接种量的增加而明显升高；但LT-01的MIC值在培养基pH值7．5以下时的pH值变化和培养基中加入血清影响不明显。MBC与杀菌曲线结果显示LT-01对葡萄球菌和链球菌有较强的杀菌作用，对肠球菌为抑菌作用，这一点也与利奈唑胺基本一致。主要代谢产物M1对革兰阳性球菌也具有体外抗菌活性，但效果为LT-01的1／2～1／16。结论LT-01作为新型恶唑烷酮类化合物，保持此类药物对革兰阳性菌，特别是耐药革兰阳性菌的较好抗菌活性的特点，其主要代谢产物也具有抗菌活性，但作用稍弱。在本次实验条件下，LT-01对临床分离致病菌的体外抗菌活性类似于利奈唑胺，值得深入研究。Objective To evaluate the in vitro antimicrobial activity of litazolid（LT-01） against bacterium isolated from clinical samples and investigate the factors affecting its antimicrobial activity, which includes bacterial loads, pH values and serum concentration of LT-01. In addition, the in vitro antimicrobial activity of the M1 metabolite of LT-01 against Gram-positive coccus was evaluated. Methods Minimum bacteriostatic concentration （MIC） of LT-01 against 859 strains of pathogenic bacterium isolated from clinical samples in the 302th hospital of PLA was determined. The MIC and minimum bactericidal concentration （MBC） were determined by agar and broth double dilution method respectively and bactericidal curves were plotted by colony counting method. Results LT- 01 had good antibacterial activity against Gram-positive bacteria including resistant strains MRSA, MRCNS, PNSSPand VRE, which was similar to that of linezolid. But LT-01 was almost ineffective for most Gram-negative bacteria. Experimental results showed that the MIC value of LT-01 was increased significantly with the increase of the amount of bacterial inoculum but was not affected by the culture medium pH value under pH of 7.5 and serum concentrations in culture. Furthermore, the results of MBC and bactericidal curve showed that LT-01 had strong sterilization effects to Staphylococcus and Streptococcus and the bacteriostatic action to enterococcus, which were also consistent with the effects of linezolid basically. The Ml-metabolite of LT-01 had in vitro antibacterial activity against Gram positive coccus, but the effects were 1/2-1/16 of LT-01.Conclusion As a new oxazolidinone-based compound, LT- 01 keeps the characteristics of good antibacterial activity against Gram-positive bacterium especially drug-resistant Gram-positive bacteria. The main metabolites of LT-O1 also had antibacterial activity with weaker effects. Under the condition of this test, in vitro antimicrobial activity of LT-01 against pathogenic bacteria isolated from clinical s

关 键 词：利他唑酮(LT-01) 恶唑烷酮类化合物 体外抗菌活性 耐药菌 

分 类 号：R978.1[医药卫生—药品]