新型糖肽类抗生素B7011对细菌感染小鼠败血症的体内抗菌作用研究

In vivo antimicrobial activities of novel glycopeptide antibiotics B7011 in murine septicemia model of bacterial infections

目的评价新型糖肽类抗生素B7011对临床分离致病菌所致小鼠败血症的体内抗菌作用。方法以耐万古霉素屎肠球菌(vanomycin-resistant Enterococci,VRE)、甲氧西林敏感金葡球菌(methicillin sensitive Staphylococcus aureus,MSSA)和耐甲氧西林金黄色葡萄球菌(methicillin resistant Staphylococcus aureus,MRSA)感染败血症小鼠为动物模型,经尾静脉注射B7011及万古霉素,比较两药对感染小鼠的保护作用。结果B7011对MSSA、MRSA、VRE感染小鼠败血症模型有明显保护作用。其ED50分别为0.722、0.193和0.395mg/kg。与万古霉素比较,在MRSA和VRE感染的小鼠败血症模型保护试验中,两药的ED50参数比较P<0.05,有显著差异;在对MSSA感染的小鼠败血症模型保护模型中,两药的ED50参数比较P>0.05,无显著差异。结论实验结果表明,B7011对革兰阳性菌有很好的抗菌作用,尤其是可以显著降低耐药菌急性感染败血症小鼠的死亡数量,其保护作用明显优于万古霉素。结合体外试验结果,说明B7011有望成为临床上应用于耐药菌感染的,具有较好疗效的新型抗生素。

Objective To evaluate in vivo antimicrobial activities of novel glycopeptide antibiotics B7011 in murine septicemia model of clinic isolated bacterial infections. Methods We researched the protective effects of B7011 and vancomycin in septicemia model of Gram-positive bacterial infections, and then we calculated and compared the ED50 and ED95 of the two drugs with DAS2.1.1. Results B7011 showed good protective effects in septicemia model of MSSA, MRSA, and VRE infections. The ED50 values against the three bacteria were 0.722, 0.193, and 0.395mg/kg, respectively. Compared to vancomycin, in protective test of septicemia model in mice infected with MRSA and VRE, the ED50 parameters of the two drugs were significantly different (P<0.05). In the protective test of septicemia in mice infected with MSSA, there was no significant difference in ED50 parameters between the two drugs (P>0.05). Conclusion The results showed that B7011 had a good antibacterial effect against Gram-positive bacteria, especially that the death amount of the mice with acute infections of the drug-resistant bacteria could be obviously reduced, and the protective effect was obviously better than vancomycin. Combined with test in vitro, the results indicate that B7011 is expected to be a new type of antibiotic which is clinically applied to drug-resistant bacteria and has a better therapeutic effect.