关键词: 泛耐药结核病, 贝达喹啉, 药物评价, 观察性研究

Abstract:

Objective To analyze the short-term effectiveness and safety of bedaquiline-containing regimen in 16 patients with multidrug-resistant tuberculosis (MDR-TB) or extensively drug-resistant tuberculosis(XDR-TB). Methods From September 2018 to January 2020, 16 patients treated with bedaquiline regimen and met the inclusion criteria in Fuzhou Pulmonary Hospital were selected, including 4 MDR-TB patients, 6 XDR-TB patients, and 6 pre-XDR-TB patients. The conversion of sputum culture for Mycobacterium tuberculosis at 24 weeks was analyzed. Changes of electro-cardiogram QTcF at 1, 2, 4, 8, 12, 16, 20, 24 weeks before enrollment and changes of chest lesions at 12 and 24 weeks after treatment were monitored, and adverse drug reactions and treatment for them were recorded. Results All of the 16 patients completed 24 weeks of intensive therapy, and the median time of sputum culture conversion was 8 (IQR:4,12) weeks. The time of conversion was 4 weeks in 2 patients, 8 weeks in 10 patients, and 12 weeks in 3 patients,1 patient was continuously positive in culture. Chest CT scan of lung lesions showed significant absorption in 7 cases, partial absorption in 7 cases, and no change in 2 cases. Adverse reactions mainly were prolonged QTcF (25.8%, 42/163), tolerable gastrointestinal reactions (22.1%, 36/163), abnormal liver function (3.7%, 6/163), hyperuricemia (36.8%, 60/163), and leukopenia (4.3%, 7/163), fatigue, joint muscle soreness (3.1%. 5/163), respiratory failure (0.6%, 1/163), and skin redness (3.7%, 6/163). The median ECG QTcF value at baseline time for those 16 patients was 412.50 (IQR: 398.25, 420.75) ms,while it changed to 414.00 (405.00, 426.75) ms at 2 weeks, 419.50 (402.00, 434.50) ms at 4 weeks, 410.50 (398.25, 421.25) ms at 8 weeks, 421.50 (409.50, 434.75) ms at 12 weeks, and 424.50 (413.75,432.25) ms at 16 weeks, 421.50 (409.50, 434.75) ms at 20 weeks and 424.00 (414.00, 435.25) ms at 24 weeks. There were statistically significant differences at 12, 16, 20 and 24 weeks comparing with the baseline (Z=-2.198,P=0.028;Z=-2.096,P=0.036;Z=-1.965,P=0.049;Z=-2.406,P=0.016). None of the 16 patients had QTcF>500ms. Conclusion The treatment regimen containing bedaquiline showed good clinical effectiveness and high safety in the treatment of MDR-TB patients, which can enrich the clinical drug selection for treating MDR-TB.

Key words: Extensively drug-resistant tuberculosis, Bedaquiline, Drug evaluation, Observational study