Abstract:

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 MIC₅₀ and MIC₉₀ 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 MIC₅₀ and MIC₉₀ 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.

Key words: GSK656, Antimicrobial agent, Mycobacteria,atypical, Drug evaluation