青蒿琥酯对大肠杆菌临床分离株抗生素敏感性的影响研究

The Effects of Artesunate on the Sensitivity of Antibiotics against Clinical Isolated Drug-resistant Escherichia coli

探讨青蒿琥酯(Artesunate,ARS)的体外抗菌活性及其与临床常用抗生素联合对临床耐药大肠杆菌(Escherichia coli,E.coli)的作用效果。采用微量肉汤稀释法测定ARS与7种抗生素分别对6株临床分离E.coli的敏感性;采用棋盘稀释法测定ARS分别与7种抗生素联合对耐药E.coli的分级抑菌浓度(fractional inhibitory concentration,FIC),判定联合抑菌效应;采用平皿打孔法测定ARS预处理对抗生素抑菌圈直径的影响。结果显示,单独使用ARS无明显抑菌作用,但当ARS≥512μg/m L时,与抗生素联用可显著降低抗生素MIC值,其中除链霉素FIC指数为0.6,表现为相加作用外,其余抗菌药FIC指数均小于0.5,表现为协同效应。使用512μg/m L和1024μg/m L ARS前处理耐药E.coli仅增加链霉素和黏菌素的抑菌圈直径。结果表明,ARS本身不具有抑菌活性,但与受测试抗生素同时使用可显著增加抗生素对耐药E.coli的抗菌效果,而ARS预处理对受测试抗生素的增敏效果有限。

The antibacterial activity of artesunate(ARS)in vitro and its effect on clinical drug-resistant Escherichia coli(E.coli)in combination with antibiotics were investigated.The sensitivity of ARS and 7 antibiotics to 6 clinical isolates of E.coli were determined by micro-broth dilution method.The fractional inhibitory concentration(FIC)of ARS combining with 7 antibiotics against resistant E.coli was determined by checkerboard dilution method.The plate perforation method was used to study the effect of ARS pretreatment on the diameter of antibiotic inhibition zone.ARS had no obvious antibacterial effect when used alone.However,when combined with antibiotics,ARS(≥512μg/m L)could significantly reduce the MIC value of antibiotics.The FIC indexes of6 antibiotics were all less than 0.5 except for streptomycin,showing synergistic effects.In addition,pretreatment by 512μg/m L and 1024μg/m L ARS increased the inhibition zone diameter of both streptomycin and colistin against resistant E.coli,with no effects to other tested antibiotics.Taken together,ARS has no inherent antibacterial activity,but it can significantly enhance the antibacterial effect of antibiotics against drug-resistant E.coli.