Republic Scientific and Practical Center of Pulmonology and Tuberculosis, Minsk.
International Union Against Tuberculosis and Lung Disease, Paris.
Monaldi Arch Chest Dis. 2021 Jan 14;91(1). doi: 10.4081/monaldi.2021.1646.
There is limited evidence describing the safety and effectiveness of bedaquiline and delamanid containing regimens in children and adolescents with Multidrug-Resistant Tuberculosis (MDR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) globally. In this nationwide descriptive cohort study from Belarus, we examined adverse drug events, time to culture conversion, treatment outcomes including post-treatment recurrence among children and adolescents (<18 years of age) treated with bedaquiline and/or delamanid containing regimens from 2015 to 2019. Of the 40 participants included (55% females; age range 10-17 years), 20 (50%) had XDR-TB and 15 (38%) had resistance to either fluoroquinolone or second-line injectable. Half of the patients received delamanid and another half received bedaquiline with one patient receiving both drugs. AEs were reported in all the patients. A total of 224 AEs were reported, most of which (76%) were mild in nature. Only 10 (5%) AEs were graded severe and one AE was graded life-threatening. A total of 7 AEs (3%) were classified as 'serious' and only one patient required permanent discontinuation of the suspected drug (linezolid). Most of the AEs (94%) were resolved before the end of treatment. All patients culture-positive at baseline (n=34) became culture-negative within three months of treatment. Median time to culture conversion was 1.1 months (interquartile range: 0.9-1.6). Two patients were still receiving treatment at the time of analysis. The remaining 38 patients successfully completed treatment. Among those eligible and assessed at 6 (n=32) and 12 months (n=27) post-treatment, no recurrences were detected. In conclusion, treatment of children and adolescents with MDR-TB and XDR-TB using bedaquiline and/or delamanid containing regimens was effective and had favourable safety profile. Achieving such excellent outcomes under programmatic settings is encouraging for other national tuberculosis programmes, which are in the process of introducing or scaling-up the use of these new drugs in their countries.
在全球范围内，仅有有限的证据描述了贝达喹啉和德拉马尼联合方案在儿童和青少年耐多药结核病（MDR-TB）和广泛耐药结核病（XDR-TB）中的安全性和有效性。在白俄罗斯进行的这项全国性描述性队列研究中，我们检查了不良药物事件、培养转换时间、治疗结局，包括在 2015 年至 2019 年间接受贝达喹啉和/或德拉马尼联合方案治疗的儿童和青少年（<18 岁）的治疗后复发。40 名参与者中（55%为女性；年龄范围 10-17 岁），20 名（50%）患有 XDR-TB，15 名（38%）对氟喹诺酮类药物或二线注射药物耐药。一半的患者接受德拉马尼治疗，另一半接受贝达喹啉治疗，一名患者同时接受两种药物治疗。所有患者均报告了药物不良反应。共报告了 224 例药物不良反应，其中大多数（76%）为轻度。只有 10 例（5%）药物不良反应被评为严重，1 例药物不良反应被评为危及生命。共有 7 例（3%）药物不良反应被归类为“严重”，只有 1 例患者需要永久停用可疑药物（利奈唑胺）。大多数（94%）药物不良反应在治疗结束前得到解决。所有基线培养阳性的患者（n=34）在治疗三个月内转为培养阴性。培养转换的中位时间为 1.1 个月（四分位距：0.9-1.6）。两名患者在分析时仍在接受治疗。其余 38 名患者成功完成治疗。在符合条件并在 6 个月（n=32）和 12 个月（n=27）时进行评估的患者中，未发现复发。总之，贝达喹啉和/或德拉马尼联合方案治疗儿童和青少年 MDR-TB 和 XDR-TB 是有效且具有良好安全性的。在方案环境下取得如此优异的结果，令人鼓舞，其他国家结核病规划正在其国家引入或扩大使用这些新药。
