Adjunctive and supportive strategies to mitigate drug toxicities in the treatment of nontuberculous mycobacterial disease with future directions.

Nontuberculous mycobacteria (NTM), particularly Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABC), are increasingly recognized as major opportunistic pathogens. Standard therapy requires prolonged multidrug regimens, often extending for more than 12 months, yet treatment success remains limited, especially for MABC. One of the greatest barriers to effective therapy is not antimicrobial resistance alone but also the high burden of drug-related toxicities. Hepatotoxicity, ototoxicity, nephrotoxicity, myelosuppression, neuropathy, gastrointestinal intolerance, and dermatologic complications frequently lead to dose reduction, interruption, or discontinuation, undermining therapeutic efficacy and patient adherence. This review summarizes current standard regimens for MAC and MABC, details the spectrum of toxicities associated with commonly used agents, and evaluates emerging supportive and adjunctive strategies. Hepatoprotective agents such as ursodeoxycholic acid, silymarin, and N-acetylcysteine, antioxidants and aspirin for aminoglycoside-related ototoxicity, liposomal inhaled amikacin as an alternative to intravenous administration, dose optimization and pyridoxine supplementation for linezolid, and prophylactic antiemetics for tigecycline represent pragmatic approaches with varying levels of evidence. While most supportive measures are extrapolated from tuberculosis cohorts or small pilot studies, they collectively highlight the potential to improve tolerability and adherence. Future research should prioritize prospective, NTM-specific trials to validate these interventions and develop structured toxicity management frameworks. By embedding supportive strategies alongside antimicrobial regimens, NTM care can move toward a more holistic paradigm that not only enhances microbiological outcomes but also improves patient quality of life.