GSK656和阿米卡星对脓肿分枝杆菌的体外联合药物敏感性研究

In vitro synergistic activities of GSK656 with amikacin against Mycobacterium abscessus

目的:评价3-氨甲基-4-卤代苯并噁唑类化合物GSK656与阿米卡星联合用药对脓肿分枝杆菌分离株的体外抑菌作用。方法:收集首都医科大学附属北京胸科医院菌株库保存的30株脓肿分枝杆菌,采用微孔阿尔玛蓝检测法(MABA法)测定GSK656和阿米卡星对脓肿分枝杆菌的体外最低抑菌浓度(MIC)。采用棋盘稀释法进行联合药物敏感性试验,通过分级抑菌浓度指数判断联合抑菌的效果。结果:GSK656对脓肿分枝杆菌的MIC为0.063~4.000 mg/L;阿米卡星对脓肿分枝杆菌的MIC为4.000~16.000 mg/L。GSK656对脓肿分枝杆菌分离株的MIC_(50)和MIC_(90)分别为0.250 mg/L和2.000 mg/L,阿米卡星对脓肿分枝杆菌分离株的MIC_(50)和MIC_(90)分别为8.000 mg/L和16.000 mg/L。GSK656与阿米卡星联合使用时,5株(16.7%)脓肿分枝杆菌分离株表现为协同作用,1株(3.3%)分离株表现为拮抗作用,其他分离株(80.0%,24/30)表现为无关作用。结论:GSK656与阿米卡星的体外联合用药对脓肿分枝杆菌表现出良好的抑菌效果,可为临床用药提供一定参考价值。

Objective:To investigate the in vitro synergistic effect of GSK656,a novel member of 3-aminomethyl 4-halogen benzoxaboroles,with aminoglycoside-amikacin against Mycobacterium abscessus.Methods:Thirty clinical M.abscessus isolates were collected from the Biobank of Beijing Chest Hospital affiliated to Capital Medical University.Minimum inhibitory concentration(MIC)were determined using microdilution MABA assay.The checkerboard titration method was used to explore the in vitro synergistic effect between GSK656 and amikacin against M.abscessus isolates.Fractional inhibitory concentration index was calculated to determine the combined effects of these two compounds.Results:GSK656 and amikacin showed potent antibacterial activities against M.abscessus.The MIC of M.abscessus ranged from 0.063 to 4.000 mg/L for GSK656,the MIC_(50) and MIC_(90) of which were 0.250 and 2.000 mg/L,respectively.The MIC ranged from 4.000 to 16.000 mg/L for amikacin,the MIC_(50) and MIC_(90) of which were 8.000 and 16.000 mg/L,respectively.For GSK656-amikacin combination,only 1 strain(3.3%)had antagonistic effect.Synergy for GSK656-amikacin combination was observed in 5 isolates(16.7%);antagonism was observed in one isolate(3.3%);while the remaining isolates(80.0%)showed indifference.Conclusion:GSK656 and amikacin holds potent antibacterial activity against M.abscessus,which provids important clinical benefit for treatment of.M.abscessus infections.