Safety, efficacy, and serum concentration monitoring of bedaquiline in Chinese patients with multidrug-resistant tuberculosis

Objectives: To determine the safety and efficacy of bedaquiline for Chinese patients with multidrug-resistant tuberculosis (MDR-TB) based on serum concentration monitoring and to identify factors associated with QTc prolongation occurring during treatment. Methods: Data were collected from 35 patients who received treatment regimens containing bedaquiline for MDR-TB from May 2018 to December 2020. Blood samples were collected, and serum concentrations of bedaquiline were measured using high-performance liquid chromatography–mass spectrometry. Results: After completing the 24-week bedaquiline treatment course, 80.0% of the patients’ sputum cultures turned negative. The median time to sputum culture conversion was 75.5 days (interquartile range 52–126 days). The mean serum concentration of bedaquiline was 0.586 ± 0.288 µg/ml during treatment and 0.205 ± 0.145 µg/ml at 16 weeks after bedaquiline discontinuation. Bedaquiline remained detectable 52 weeks after discontinuation. Combination with clofazimine during bedaquiline treatment significantly increased cardiac QTc prolongation. When QTc prolongation occurred, serum potassium levels decreased by 10.71% from baseline, while serum sodium levels increased by 1.07% from baseline. Conclusions: Good treatment outcomes were obtained with bedaquiline treatment in Chinese patients with MDR-TB. Combination with clofazimine increased the risk of QTc prolongation. Serum electrolytes (potassium and sodium) should be measured regularly during treatment of MDR-TB with regimens containing bedaquiline