Anti-Mycobacterium avium complex activity of clarithromycin, rifampin, rifabutin, and ethambutol in combination with adenosine 5′-triphosphate

•In vitro anti-MAC activity of CLA+ rifamycin and CLA+ EMB was increased by ATP.•ATP-mediated synergistic activity was expressed in a strain-dependent manner.•In vitro regrowth of drug-treated bacteria was delayed by combined use of ATP.

We previously reported that adenosine 5′-triphosphate (ATP) inhibited the growth of various bacteria, including mycobacteria, Staphylococcus, and Pseudomonas, without damaging bacterial surface structures. Notably, ATP's antibacterial activity was found to be attributable to its iron-chelating ability. ATP exhibited combined effects with some antimicrobials against Mycobacterium intracellulare and methicillin-resistant S. aureus, suggesting its usefulness as an adjunctive drug in the chemotherapy against certain intractable infections. In this study, we examined detailed profiles of the anti-Mycobacterium avium complex (MAC) activity of some antimicrobial agents, including clarithromycin (CLA), rifampin (RIF), rifabutin (RBT), and ethambutol (EMB), in combination with ATP. It was found that the anti-MAC activity of CLA + RIF, CLA + RBT, and CLA + EMB was markedly potentiated in a strain-dependent manner. In this case, the onset of the regrowth of antimicrobial agent-treated mycobacteria during cultivation was significantly delayed in the presence of ATP, indicating the usefulness of ATP as an adjunctive drug in chemotherapy against MAC infections.