The effects of bedaquiline and fluoroquinolone-based treatment regimens in patients with MDR/XDR-TB on QT prolongation

Abstract

Aim: To evaluate the effects of bedaquiline and fluoroquinolone-based treatment regimens in patients with MDR/XDR-TB on QT prolongation

Methods: A prospective cohort study including 87 patients was conducted. All patients underwent a standard ECG prior to adding bedaquiline to the chemotherapy course and once every 4 weeks subsequently (at the end of Weeks 4, 8, 12, 16, 20, 24). QTc intervals and blood potassium levels were measured at these time points. All subjects were divided into 2 groups: 1 group - 24 patients with QTc prolongation (over 450 ms), 2 group - 63 patients with normal QTc values

Results: During treatment, QTc prolongation of 450 to 500 ms was observed in 27.6% patients (group 1), most frequently at the end of Week 12 of chemotherapy. In group 1, QTc interval returned to normal in 90.7% of patients: after 4 to 8 weeks in 54.2% of patients and after 12 to 16 weeks in 36.5% of patients. In group 1, mean QTc values before and after bedaquiline therapy were 434 and 446 ms, respectively. The longest QTc interval was observed at the end of Weeks 8 and 12 (450 and 446 ms, respectively). In the group 2, the QTc interval values were lower (p<0.01), were within the normal range at all follow-up time points, and did not change during chemotherapy

Conclusions: During tuberculosis treatment, QTc prolongation of 450 to 500 ms was observed in 27.6% patients with MDR/XDR-TB, primarily at the end of Week 12 of therapy, was not associated with clinical manifestations or ECG-signs of ventricular arrhythmia, and did not require additional therapeutic measures in any of the cases. In 90.7% of patients, QTc interval returned to normal values