Bedaquiline for the Treatment of Pulmonary Non-tuberculous Mycobacterial Infections: Retrospective Analysis From a Large Healthcare System

Abstract Rationale: Pulmonary infections from non-tuberculous mycobacteria (NTM) cause significant morbidity and mortality, particularly among patients with underlying lung disease. NTM species are typically drug-resistant, requiring prolonged multi-drug antimicrobial courses with significant toxicities and high microbiologic recurrence rates. Bedaquiline, a diarylquinoline approved for the treatment of multidrug-resistant tuberculosis, has been shown to have bacteriostatic activity against NTM and appears clinically effective in small case series. We aimed to describe clinical characteristics, tolerability, and treatment outcomes in patients treated with bedaquiline for pulmonary NTM at the Mass General Brigham (MGB) healthcare system. Methods: The study was approved by the MGB Institutional Review Board. Electronic medical records were manually reviewed to include all patients treated with bedaquiline between January 2012 through December 2023 for culture-positive pulmonary NTM infection. Kaplan-Meier estimates were used for duration of treatment and survival. Results: There were 34 patients treated with bedaquiline for NTM infection, of which 24 patients had pulmonary NTM and were included in this analysis. Median age at treatment initiation was 58.5 years (IQR 44, 64). 6 patients (25%) were male and 18 patients (75%) were female. 6 patients (25%) were immunocompromised. 6 patients (25%) had cystic fibrosis (CF), 11 patients (46%) had non-CF bronchiectasis, and 4 patients (21%) had other underlying lung conditions. Cavitary disease was present in 14 patients (61%). 15 (63%) had Mycobacterium avium complex and 12 (50%) had Mycobacterium abscessus. 4 patients (17%) had a dual NTM infection with more than 1 species. Bedaquiline was used as salvage therapy for 15 patients (62.5%) and as oral-stepdown from an IV regimen for 9 patients (37.5%). Median time from first positive culture to any NTM treatment was 3.0 months (IQR 0.5, 14) and median time from first positive culture to bedaquiline usage was 41.5 months (IQR 24, 77.8). Six patients (25%) underwent surgery in addition to medical management. Among the 20 patients with longitudinal microbiologic follow-up, 9 (45%) achieved culture conversion. 4 patients stopped bedaquiline due to drug intolerance (3 with nausea, 1 with QTc prolongation), yet 1 later resumed. Conclusion: This is the largest case series reported to date on the use of bedaquiline for pulmonary NTM. While limited by the retrospective nature and single healthcare system experience, this analysis suggests bedaquiline may have clinical efficacy when included in a multidrug treatment regimen in a group of advanced NTM patients with limited treatment options. Further analysis in larger cohorts is warranted.