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

关键词:  青蒿琥酯，抗生素敏感性，耐药大肠杆菌

Key words:  artesunate  sensitivity of antibiotics  drug-resistant E. coli

摘要:

目的 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。方法 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 单独使用ARS 5120 μg /mL以上无明显抗抑菌作用,但当ARS≥512 μg /mL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。另外,使用512 μg /mL 和1024 μg /mL ARS前处理耐药E. coli仅增加链霉素和黏菌素的抑菌圈直径。结论 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。

Abstract:

Objectives: 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. Methods: 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 was determined by plate perforation method. Results: ARS had no obvious antibacterial effect when used alone. However, when combined with antibiotics, ARS (≥512 μg/mL) could significantly reduce the MIC value of antibiotics. The FIC indexes of 6 antibiotics were all less than 0.5 except for streptomycin, showing synergistic effects. In addition, pretreatment by 512 μg/mL and 1024 μg/mL ARS increased the inhibition zone diameter of both streptomycin and colistin against resistant E. coli, with no effects to other tested antibiotics. Conclusion: ARS has no inherent antibacterial activity, but it can significantly enhance the antibacterial effect of antibiotics against drug-resistant E. coli.