Triple antimicrobial combinations with potent synergistic activity against <i>M. abscessus</i>

Synergy of antimicrobial combinations was tested against contemporary <i>Mycobacteroides abscessus</i> 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 <i>M. abscessus</i> subsp. <i>abscessus</i> and <i>M. abscessus</i> subsp. <i>bolletii</i> isolates were fully sensitized to azithromycin at the FIC index, as were isolates with elevated clofazimine MICs.