Triple antimicrobial combinations with potent synergistic activity against M. abscessus.

Synergy of antimicrobial combinations was tested against contemporary Mycobacteroides abscessus isolates using 2D and 3D checkerboard assays. Triple combinations of omadacycline-azithromycin-clofazimine, tigecycline-azithromycin-clofazimine, omadacycline-azithromycin-linezolid, and omadacycline-azithromycin-contezolid demonstrated synergy (fractional inhibitory concentration index ≤ 0.5) against 33%, 31%, 62%, and 66% of isolates, respectively. Notably, in all triple combinations, macrolide-resistant M. abscessus subsp. abscessus and M. abscessus subsp. bolletii isolates were fully sensitized to azithromycin at the FIC index, as were isolates with elevated clofazimine MICs.