Abstract Background Treatment intensification for Mycobacterium avium complex (MAC) pulmonary disease typically entails initiation of amikacin for patients with persistent sputum culture positivity after six months of standard therapy but may be complicated by moderate intolerance and limited therapeutic efficacy. Emerging evidence suggests potential anti-mycobacterial synergy between inhaled amikacin and oral clofazimine, raising interest in new combinatory strategies for refractory disease. We describe clinical outcomes associated with clofazimine-amikacin regimens for the treatment of pulmonary MAC. Methods This study was approved by the Mass General Brigham (MGB) Institutional Review Board. We included all patients treated with oral clofazimine and either intravenous (IV) or inhaled amikacin for culture-confirmed pulmonary MAC from August 2011 through August 2025. Electronic medical records were manually reviewed for demographic, microbiologic, and clinical data. Results Twenty-four patients with pulmonary MAC received both clofazimine and amikacin. Median age at treatment initiation was 63.0 years; 20 (83.3%) were female and median BMI was 22.5. Cavitary disease was present in 20 (83.3%) and bronchiectasis in all 24 (100%); 5 (20.8%) had M. abscessus co-infection. Clofazimine was part of initial therapy in 2 (8.3%) and salvage therapy in 22 (91.7%), initiated a median of 15.2 months (IQR: 8.3–70.0) after treatment start. Bedaquiline was used in 6 (25.0%). Five (20.8%) received IV amikacin, 11 (45.8%) received inhaled amikacin, and 8 (33.3%) received IV followed by inhaled formulation. Among 18 patients with post-clofazimine respiratory cultures, 10 (55.6%) achieved culture clearance, 4 (40.0%) of whom reverted (3 during clofazimine therapy, one after end of therapy). Four (16.7%) had persistent culture positivity beyond six months. Of 18 patients with follow-up imaging, 10 (55.6%) showed radiographic improvement. As of August 2025, 13 (54.2%) had discontinued clofazimine (median duration 12.7 months; IQR: 5.8–43.6). Only one patient required permanent discontinuation due to gastrointestinal intolerance. Overall, 12 (50.0%) patients completed and discontinued MAC therapy (median duration 32.7 months; IQR: 15.6–141.6). Among these, 4 died post-treatment (2 with active pulmonary NTM disease at death), 1 restarted therapy, and 7 (58.3%) had no microbiologic recurrence. Conclusion Combined clofazimine-amikacin therapy was well-tolerated and associated with microbiologic and radiographic improvement in many patients with pulmonary MAC, including those receiving it as salvage therapy. These findings support the potential utility of clofazimine–amikacin regimens for refractory disease, though validation in larger, prospective studies is warranted. This abstract is funded by: None
Hysell et al. (Fri,) studied this question.