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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Therapeutic Advances in Mycobacterium avium Complex Pulmonary Disease: Current Treatments and Emerging Host-Directed Approaches

  1. 1College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 E. Second St., Pomona, CA 91766-1854, USA

Abstract

Mycobacterium avium complex (MAC) is the leading cause of non-tuberculous mycobacterial (NTM) pulmonary disease, with increasing incidence among aging and immunocompromised populations. Despite guideline-recommended multidrug therapy consisting of a macrolide, ethambutol, and a rifamycin, treatment remains prolonged and complicated by incomplete culture conversion, adverse effects, recurrence, and antimicrobial resistance. Intracellular persistence, biofilm formation, and intrinsic resistance mechanisms further challenge disease management. This review summarizes MAC pathogenesis, host immune responses, current treatments, and emerging therapeutic strategies. Promising approaches include novel antimicrobial agents, optimized multidrug regimens, drug repurposing, inhaled delivery systems, and host-directed therapies. Particular emphasis is placed on glutathione (GSH), an intracellular antioxidant with immunomodulatory properties, as a potential adjunctive therapy. Experimental studies suggest that GSH and its precursor N-acetylcysteine may influence oxidative stress, inflammatory responses, and antimycobacterial activity. However, MAC-specific evidence remains primarily in vitro, and clinical efficacy in MAC pulmonary disease has not been established. Findings from related mycobacterial infections provide mechanistic insights but cannot be directly extrapolated to MAC pulmonary disease. Further preclinical and clinical studies are needed to determine whether GSH-based interventions can safely complement conventional antimicrobial therapy and improve treatment outcomes.

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BibTeX
@article{khachatourian2026therapeutic,
  title = {{Therapeutic Advances in Mycobacterium avium Complex Pulmonary Disease: Current Treatments and Emerging Host-Directed Approaches}},
  author = {Nooneh Melody Khachatourian and Rubina Takhmazian and Vishwanath Venketaraman},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = nov,
  doi = {10.3390/ijms27219872},
  url = {https://www.mdpi.com/1422-0067/27/21/9872},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Therapeutic Advances in Mycobacterium avium Complex Pulmonary Disease: Current Treatments and Emerging Host-Directed Approaches
AU  - Nooneh Melody Khachatourian
AU  - Rubina Takhmazian
AU  - Vishwanath Venketaraman
PY  - 2026
DA  - 2026/11/04
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219872
UR  - https://www.mdpi.com/1422-0067/27/21/9872
AB  - Mycobacterium avium complex (MAC) is the leading cause of non-tuberculous mycobacterial (NTM) pulmonary disease, with increasing incidence among aging and immunocompromised populations. Despite guideline-recommended multidrug therapy consisting of a macrolide, ethambutol, and a rifamycin, treatment remains prolonged and complicated by incomplete culture conversion, adverse effects, recurrence, and antimicrobial resistance. Intracellular persistence, biofilm formation, and intrinsic resistance mechanisms further challenge disease management. This review summarizes MAC pathogenesis, host immune responses, current treatments, and emerging therapeutic strategies. Promising approaches include novel antimicrobial agents, optimized multidrug regimens, drug repurposing, inhaled delivery systems, and host-directed therapies. Particular emphasis is placed on glutathione (GSH), an intracellular antioxidant with immunomodulatory properties, as a potential adjunctive therapy. Experimental studies suggest that GSH and its precursor N-acetylcysteine may influence oxidative stress, inflammatory responses, and antimycobacterial activity. However, MAC-specific evidence remains primarily in vitro, and clinical efficacy in MAC pulmonary disease has not been established. Findings from related mycobacterial infections provide mechanistic insights but cannot be directly extrapolated to MAC pulmonary disease. Further preclinical and clinical studies are needed to determine whether GSH-based interventions can safely complement conventional antimicrobial therapy and improve treatment outcomes.
SN  - 1422-0067
ER  -