With the application of
bedaquiline (Bdq), the success rate of
multidrug-resistant tuberculosis (MDR-TB) treatment has been significantly improved; however, the cardiac safety of the patients during treatment cannot be ignored. Hence, this study compared the effects of
bedaquiline alone and
bedaquiline combined with
fluoroquinolones (FQs) and/or
clofazimine (CFZ) on the QT interval. This single-center retrospective cohort study analyzed the clinical data of MDR-TB patients treated with
bedaquiline for 24 weeks from January 2020 to May 2021 in Xi'an Chest Hospital and compared the changes in QTcF between the two groups. Eighty-five patients were included in the study and grouped by types of anti-TB drugs affecting the QT interval they used. Group A included
bedaquiline (n = 33), and group B included
bedaquiline in combination with
fluoroquinolones and/or
clofazimine (n = 52). Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 2.4% (2/85) experienced a postbaseline QTcF of ≥500 ms, and 24.7% (21/85) had at least one change of QTcF of ≥60 ms from baseline. In group A, 9.1% (3/33) had at least one ΔQTcF of >60 ms, as did 34.6% (18/52) of group B. Multivariate Cox regression analysis showed that the adjusted risk of QT prolongation was 4.82 times higher in group B (95% confidence interval [CI], 1.406 to 16.488).
Bedaquiline combined with other anti-TB drugs affecting QT interval significantly increased the incidence of grade 3 or 4 QT prolongation; however, no serious ventricular
arrhythmia and permanent
drug withdrawal occurred. The use of
bedaquiline combined with
fluoroquinolone and/or
clofazimine is an independent risk factor affecting QT interval. IMPORTANCE
Tuberculosis (TB) is a chronic
infectious disease caused by Mycobacterium tuberculosis. The emergence of MDR-TB is caused by an organism that is resistant to at least
isoniazid and
rifampin and is currently considered the major challenge for the global control of TB.
Bedaquiline is the first new TB
drug in 50 years with a unique mechanism of action, strong anti-M.
tuberculosis activity. Yet unexplained excess deaths in the
bedaquiline arms have been found in some phase II clinical trials; thus, the FDA has issued a "boxed warning." However, the cardiac safety of the patients during treatment cannot be ignored. Accordingly, further investigations are needed to establish whether
bedaquiline combined with
clofazimine,
fluoroquinolones, or anti-TB drugs affecting the QT interval in a long-course or short-course treatment increases the risk of QT prolongation.