Skrahina Alena, Hurevich Hennadz, Falzon Dennis, Zhilevich Liudmila, Rusovich Valiantsin, Dara Masoud, Setkina Svetlana
Republican Scientific and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus.
Republican Scientific and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus.
Int J Mycobacteriol. 2016 Dec;5 Suppl 1:S62-S63. doi: 10.1016/j.ijmyco.2016.11.014. Epub 2016 Nov 23.
BACKGROUND/OBJECTIVE: Outcomes of treatment for multidrug-resistant tuberculosis (MDR-TB) remain poor worldwide. Among patients with MDR-TB in Belarus who started treatment in 2012, only 54% completed it successfully, with treatment failure reported in 22% of the patients; additionally, 11% died and 13% were lost to follow-up or remained unevaluated. In Belarus, to improve outcomes, bedaquiline was introduced in MDR-TB treatment in June 2015. The national TB program developed measures to monitor safety and effectiveness of bedaquiline-containing regimens in line with the World Health Organization recommendations.
After enrollment of patients, clinical, radiological, laboratory, and microbiological data were carefully collected at start, during treatment, and at follow-up. A total of 197 patients were enrolled: male, 140 (71%); female, 57 (29%); new TB cases, 83 (42%); previously treated, 114 (58%); extensively drug-resistant-TB (XDR-TB), 128 (65%), pre-XDR-TB (fluoroquinolone resistant), 34 (17%), pre-XDR-TB (injectables resistant), 25 (13%), and other MDR-TB cases, 10 (5%).
According to the intermediate analysis, 186 patients currently are continuing with the treatment, two patients died, and nine patients were lost to follow-up. Sputum culture conversion were observed in 186 patients (94%) at 6months and one (0.5%) of these 197 patients started treatment; six patients (3%) remain sputum culture positive. The safety data were as follows: 135 patients (68%) experienced metabolism and nutrition disorders (hyperuricemia being the most common), 127 patients (64%) experienced hepatobiliary disorders (hepatic functions abnormality being the most common), 93 patients (47%) experienced electrolyte disorders (hypomagnesemia being the most common), 80 patients (41%) experienced cardiac disorders (abnormal electrocardiogram and arrhythmia being the most common), 68 patients (35%) experienced gastrointestinal system disorders (nausea, vomiting, and abdominal pain being the most common disorders), 54 patients (27%) experienced blood and the lymphatic system disorders (low platelet count being the most common), 42 patients (21%) experienced renal and urinary disorders (creatinine clearance decrease being the most common), 40 patients (20%) experienced nervous system disorders (headache, dizziness, and paresthesia being the most common ones), 36 patients (18%) experienced skin and subcutaneous tissue disorders (rush and pruritus being the most common), 35 patients (17%) experienced ear and labyrinth disorders (tinnitus and decreased hearing being the most common ones), 32 patients (15%) experienced psychiatric disorders (insomnia being the most common disorder), and 30 patients (14%) experienced infections and infestations (candidiasis being the most common). The most adverse events were mild or moderate in severity and reversible. One death was possibly related to MDR-TB therapy.
Our interim results on safety and effectiveness of bedaquiline-containing regimens in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) patients are encouraging. They will add value to understanding role and place of this new anti-TB drug in M/XDR-TB treatment.
背景/目的：在全球范围内，耐多药结核病（MDR-TB）的治疗效果仍然不佳。在白俄罗斯，2012年开始治疗的MDR-TB患者中，只有54%成功完成治疗，22%的患者治疗失败；此外，11%的患者死亡，13%的患者失访或未得到评估。在白俄罗斯，为改善治疗效果，2015年6月在MDR-TB治疗中引入了贝达喹啉。国家结核病项目根据世界卫生组织的建议制定了监测含贝达喹啉治疗方案安全性和有效性的措施。
患者入组后，在开始治疗、治疗期间和随访时仔细收集临床、放射学、实验室和微生物学数据。共纳入197例患者：男性140例（71%）；女性57例（29%）；新发结核病病例83例（42%）；既往接受过治疗的114例（58%）；广泛耐药结核病（XDR-TB）128例（65%），预广泛耐药结核病（对氟喹诺酮耐药）34例（17%），预广泛耐药结核病（对注射剂耐药）25例（13%），其他MDR-TB病例10例（5%）。
根据中期分析，目前有186例患者继续治疗，2例患者死亡，9例患者失访。197例开始治疗的患者中，186例（94%）在6个月时痰培养转阴，1例（0.5%）仍为阳性；6例（3%）患者痰培养仍为阳性。安全性数据如下：135例患者（68%）出现代谢和营养紊乱（最常见的是高尿酸血症），127例患者（64%）出现肝胆系统紊乱（最常见的是肝功能异常），93例患者（47%）出现电解质紊乱（最常见的是低镁血症），80例患者（41%）出现心脏紊乱（最常见的是心电图异常和心律失常），68例患者（35%）出现胃肠道系统紊乱（最常见的是恶心、呕吐和腹痛），54例患者（27%）出现血液和淋巴系统紊乱（最常见的是血小板计数低），42例患者（21%）出现肾脏和泌尿系统紊乱（最常见的是肌酐清除率降低），40例患者（20%）出现神经系统紊乱（最常见的是头痛、头晕和感觉异常），36例患者（18%）出现皮肤和皮下组织紊乱（最常见的是皮疹和瘙痒），35例患者（17%）出现耳和迷路紊乱（最常见的是耳鸣和听力下降），32例患者（15%）出现精神障碍（最常见的是失眠），30例患者（14%）出现感染和寄生虫感染（最常见的是念珠菌病）。大多数不良事件为轻度或中度，且可逆转。1例死亡可能与MDR-TB治疗有关。
我们关于含贝达喹啉治疗方案在耐多药和广泛耐药结核病（M/XDR-TB）患者中的安全性和有效性的中期结果令人鼓舞。它们将有助于理解这种新型抗结核药物在M/XDR-TB治疗中的作用和地位。
