Abstract:

Objective: To analyze the adverse reactions of bedaquiline combined with conventional anti-tuberculosis drugs in the treatment of drug-resistant pulmonary tuberculosis, so as to provide basis for the safe use and monitoring of bedaquiline. Methods: A retrospective study was conducted in 127 patients with multidrug-resistant tuberculosis, pre-extensive drug-resistant pulmonary tuberculosis, extensively drug-resistant pulmonary tuberculosis and rifampicin-resistant pulmonary tuberculosis from the Drug-Resistant Tuberculosis Ward of Shandong Public Health Clinical Center. All of them completed 24-week treatment and follow-up from November 2018 to December 2020. And 66 patients treated with bedaquiline containing regimen were considered as the observation group, the other 61 patients treated without bedaquiline containing regimen were considered as the control group. Clinical data including age, gender, drug resistance type, whether or not complicated with diabetes mellitus, whether or not take other drugs that led to prolonged QTc interval, etc., were collected. The occurrence of adverse drug reactions in the treatment of the two groups was monitored, and the influencing factors of QTc interval prolongation (>450 ms) in the observation group were analyzed. Results: The incidence of QTc interval prolongation in the observation group was 48.5% (32/66), which was significantly higher than that in the control group (26.2% (16/61)) (χ²=6.678, P=0.001). There were 3 cases (4.5%) and 1 case (1.6%) with QTc interval >500 ms in the observation group and the control group, respectively. The difference was not statistically significant (Fisher exact probability method, P=0.143). There was no difference in the occurrence of other adverse drug reactions between the two groups. The QTc interval in the observation group gradually increased with the use time of the treatment regimen containing bedaquiline. At the end of the 4th week, the QTc interval was (435.1±28.8) ms, which was significantly higher than that in the baseline period ((419.0±23.2) ms) (t=3.477, P=0.001), and the peak appeared at the end of the 12th week ((439.5±30.7) ms). Multivariate analysis showed that, if treated with bedaquiline containing regimen, the risk of QTc interval prolongation in patients aged ≥45 years was 9.027 times (95%CI: 1.033-78.859) of that in patients aged 18-45 years; combined use of other drugs that can lead to QTc interval prolongation was also an independent risk factor for QTc interval prolongation (OR (95%CI)=9.033 (1.042-78.326)). Conclusion: The incidence of QTc interval prolongation increased in patients with drug-resistant pulmonary tuberculosis after treatment with bedaquiline containing regimen, but there was no serious adverse cardiac events. The incidence of adverse events in other systems did not increase. Elderly patients were at high risk of QTc interval prolongation.

Key words: Tuberculosis,pulmonary, Tuberculosis,multidrug-resistant, Drug toxicity, Bedaquiline