Bedaquiline combined with clofazimine as salvage therapy for 11 patients with nontuberculous mycobacterial lung disease.

Objective: We aimed to investigate the efficacy and safety of a regimen combining bedaquiline and clofazimine in the treatment of refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex(MAC) or Mycobacterium abscessus subsp. abscessus (here Mab).

Methods: In this open-label, prospective pilot study, patients with refractory non-tuberculous mycobacterial pulmonary disease (NTM-PD) were enrolled to receive a regimen of bedaquiline and clofazimine alongside individualized background therapies. No control group was established in the study. Sputum samples were collected for culture at baseline (prior to treatment initiation) and then monthly thereafter. After the initial 6-month period, sputum collection frequency was reduced to every two months until trial completion. The primary end-point was sputum culture conversion rate. However, due to insufficient patient enrollment, we present these findings as a case series.

Results: A total of 11 patients were enrolled in this study, including 8 cases infected with Mycobacterium abscessus subsp. abscessus, 2 with Mycobacterium avium, and 1 with Mycobacterium intracellulare. Nine patients were resistant to clarithromycin. All 11 patients completed 18 months of follow-up. After 6 months of treatment, 45% (5/11) patients achieved culture conversion. However, after 18 months' treatment, only 27% (3/11) maintained culture conversion. Chest CT imaging showed improvement in 5 patients, stability in 4 patients, and progression of lesions in 2 patients. The longest duration of bedaquiline use was 20 months. QTc interval prolongation was observed in 64% (7/11) of patients within 24 weeks, leading to permanent discontinuation of bedaquiline in one patient. The minimum inhibitory concentration (MIC) of bedaquiline ranged from ≤ 0.06 to 0.25 µg/mL prior to treatment, and two patients experienced an increase in MIC from ≤ 0.06 µg/mL to 0.12 µg/mL after treatment. The MICs of clofazimine were between 0.06 and 1 µg/mL.

Conclusion: The combination of bedaquiline and clofazimine may offer some clinical benefit in selected cases of advanced Mab and MAC lung diseases, but larger controlled studies are needed to confirm these preliminary findings.

Trial registration: This clinical study (ChiCTR2000037403) was registered on the ‌Chinese Clinical Trial Registry‌ website ( http://www.chictr.org.cn ) on ‌August 28, 2020‌.