头孢硫脒对细菌感染小鼠败血症的体内抗菌作用  

In vivo antibacterial effect of cefathiamidine against mouse septicemia

作　　者：钟巍[1] 李耘[1] 吕媛[1] 李曼宁[1] 刘健[1] 曲春明[1] ZHONG Wei, LI Yun, LU Yuan, LI Man - ning, LIU Jian, QU Chun -ming(Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034 , China)

机构地区：[1]北京大学第一医院临床药理研究所,北京100034

出　　处：《中国临床药理学杂志》2018年第7期857-860,865,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价头孢硫脒对细菌感染小鼠败血症的体内抗菌作用。方法以最小致死剂量(MLD)细菌0.5 mL感染小鼠,建立小鼠败血症动物模型。尾静脉注射不同浓度药物0.2 mL,其中头孢硫脒、头孢唑啉、氨苄西林为2次给药,间隔12 h;头孢曲松和左氧氟沙星维持1次给药。记录给药后1~7 d内小鼠的成活率,用双层综合系统综合(BLISS)法计算半数有效量(ED50)、95%有效剂量(ED95),比较头孢硫脒与对照药品之间抗菌作用的差异。对3株标准菌株及7株临床分离致病菌采用单次给药方式进行了体内保护作用实验。结果头孢硫脒对肺炎链球菌、粪肠球菌均有较好的体内抗菌活性,单次给药ED50值在1.43~11.71 mg·kg^(-1),与左氧氟沙星相似,显著优于头孢唑啉。对于肺炎链球菌、金黄色葡萄球菌和流感嗜血杆菌,头孢硫脒ED50值在0.78~14.78mg·kg^(-1),均较单次给药明显下降。但对于粪肠球菌,2次给药的ED50值较单次给药有所上升,可能与血药浓度过低而影响体内保护作用有关。结论头孢硫脒对革兰氏阳性菌具有较好体内抗菌作用,特别对于肺炎链球菌和粪肠球菌。对于大多数菌种,头孢硫脒每天2次或多次给药更为合理。Objective To evaluate the in vivo antibacterial effect of cefathiamidinein against mouse septicemia. Methods Experimental model of mouse septicemia was established by intraperitoneally injection with 0. 5 mL minimum lethal dose （MLD） bacteria. The 0, 2 mL different concentrations of drugs were injected through caudal vein. Cefathiami- dine, cefazolin and ampicillin adopted two methods of dose regimen, which are single -dose and two -dose; while, both ceftriaxone and levo- floxacin adopted single - dose. The survival time of the infected mouse was monitored for 1 - 7 d. The 50% , 95% effective doses（ED50,ED50 ） were determined by the Bi - level integrated system synthesis （BLISS） method. The antibacterial activities between ceftazine and control drugs were compared. In vivo protection experiments were carried out on 3 stan- dard strains and 7 pathogenic strains isolated through single dose. Results The cefathiamidine had good antibacterial activity in vivo against Strep- tococcus pneumonia and Enterococcus faecalis. The ED50 of single - dose was between 1.43 - 1.71 mg·kg-1, which was significantly superior to cefazolin and was similar to levofloxacin. According to the results of two -dose regimen, the EDso values of cefathiamidine against Sreptococcuspneumonia, Staphylococcus aureus and Haemophilus influenza significantly declined, which were between 0.78 - 14.78 mg·kg-1. However, with regard to Enterococcus faecalis, the ED50 value of two - dose increased compared to that of single- dose, which could be related to the fact that low plasma concentration affected protective effects in vivo. Conclusion Cefathiamidine had a better antibacteria effect in vivo against gram - positive bacteria, especially Strepto- coccus pneumonia and Enterococcus faecalis. Through the comparison between single - dose and two - dose, it is more reasonable to adopt two - dose or multiple - dose of cefathiamidine with regard to most strains.

关 键 词：头孢硫脒 败血症模型 体内抗菌作用 临床分离致病菌 

分 类 号：R978.1[医药卫生—药品]