Failure with acquired resistance of an optimised bedaquiline-based treatment regimen for pulmonary Mycobacterium avium complex disease

Abstract

To the Editor: 5 years ago, a then 50-year-old woman presented with long-standing fatigue, dyspnoea and a chronic productive cough. Based on a computed tomography scan of the thorax and multiple positive cultures, she was diagnosed with nodular-bronchiectatic Mycobacterium avium pulmonary disease; she was also found to have a heterozygous F508del CFTR gene mutation. She commenced therapy with rifabutin 300 mg once daily, ethambutol 1200 mg once daily and azithromycin 500 mg once daily. After 15 months of ongoing symptoms, radiographic deterioration and persistent culture positivity, clofazimine 100 mg once daily and thrice weekly intravenous amikacin 15 mg•kg −1 were added to the regimen. Amikacin was halted after 4 months; the remaining four drugs were continued. The dose of azithromycin was lowered to 250 mg once daily after 9 months because of hearing loss.

Recent advances in nontuberculous mycobacterial lung infections

“…A study of bedaquiline as salvage therapy in 10 patients with refractory MAC or M. abscessus lung disease showed a clinical and microbiologic response in the majority of patients, although none achieved sustained culture conversion 67 . Subsequent studies have demonstrated the emergence of bedaquiline-resistant isolates 68, 69 , including seven of 16 bedaquiline-treated patients 69 . Bedaquiline may cause QT prolongation and other toxicity.…”

Efficacy of Bedaquiline, Alone or in Combination with Imipenem, against Mycobacterium abscessus in C3HeB/FeJ Mice

“…However, efficient responses to BDQ were observed in other animal models, such as zebrafish (12). Two studies reported poor or negative results for BDQ administration against nontuberculous mycobacteria-infected patients (27,28). However, recent studies showed that the activity of BDQ can be potentiated with adjunctive therapy, thus improving BDQ-based treatments (16,29).…”

Successful bedaquiline-containing antimycobacterial treatment in post-traumatic skin and soft-tissue infection by Mycobacterium fortuitum complex: a case report

“…Emergence of resistance is a key problem in NTM treatment. Zweijpfenning et al have recently published a case where an increase in the bedaquiline MIC led to a resistant phenotype (or sub-population) of Mycobacterium avium complex resulting in failure of a bedaquilinebased treatment regimen [45]. We therefore believe that the combination with a highly active flourochinolon to efficiently suppress mycobacterial growth and the preceding intravenous induction therapy are key elements of successful treatment.…”