South Africa Medical Research Council (SAMRC) Centre for Tuberculosis Research DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, South Africa.
Bacterial Diseases Service, Operational Direction Communicable and Infectious Diseases, Scientific Institute of Public Health (WIV-ISP), Brussels, Belgium.
J Antimicrob Chemother. 2018 Oct 1;73(10):2667-2674. doi: 10.1093/jac/dky248.
Use of the Xpert MTB/RIF assay has increased the number of people diagnosed with rifampicin-resistant tuberculosis (RR-TB), especially in South Africa where Xpert is now the initial diagnostic for individuals with TB symptoms. We hypothesized that a proportion of RR-TB patients determined by Xpert can be treated with a rifabutin-containing regimen.
Rifabutin susceptibility by rpoB mutation was assessed in 349 individuals from South Africa and 172 from Belgium. rpoB polymorphisms were identified by Sanger sequencing. Rifampicin and rifabutin susceptibility was assessed phenotypically. A systematic review was performed to comprehensively collate information on rifabutin susceptibility by rpoB polymorphism. Rifabutin susceptibility was assigned to rpoB polymorphisms based on their positive likelihood ratios and ORs.
One hundred and twelve rpoB polymorphisms (67.9% from literature) were identified from all 2045 RR-TB patients, of which 17 polymorphisms could be classified as susceptible/resistant to rifabutin. Eleven polymorphisms were associated with rifabutin susceptibility. The 516GTC mutation was the most common, representing 70% (South Africa) and 76% (Belgium) of all rifabutin-susceptible isolates. At a population level, the 11 polymorphisms associated with rifabutin susceptibility occurred in 33.2% and 16.6% of all South African and Belgian patients diagnosed with RR-TB, respectively.
Identification of the exact rpoB polymorphism leading to the diagnosis of RR-TB has the potential to allow inclusion of rifabutin in the treatment regimen of a substantial proportion of RR-TB patients. A randomized controlled trial evaluating the efficacy of a rifabutin-containing TB treatment regimen in these selected patients is needed to provide the evidence required for a change in policy.
使用 Xpert MTB/RIF 检测法增加了利福平耐药结核病 (RR-TB) 的诊断人数，尤其是在南非，Xpert 现在是有结核病症状的个体的初始诊断方法。我们假设，Xpert 确定的一部分 RR-TB 患者可以用含利福布汀的方案治疗。
评估了来自南非的 349 名和来自比利时的 172 名个体中利福布汀的 rpoB 突变的敏感性。通过 Sanger 测序鉴定 rpoB 多态性。通过表型评估利福平利福布汀的敏感性。进行了系统评价，全面收集 rpoB 多态性导致利福布汀敏感性的信息。根据阳性似然比和 OR ，将利福布汀敏感性分配给 rpoB 多态性。
从所有 2045 例 RR-TB 患者中鉴定出了 121 个 rpoB 多态性（67.9%来自文献），其中 17 个多态性可分为利福布汀敏感/耐药。有 11 个多态性与利福布汀敏感性相关。516GTC 突变最常见，占南非（70%）和比利时（76%）所有利福布汀敏感分离株的 70%。在人群水平上，与利福布汀敏感性相关的 11 个多态性分别发生在南非和比利时诊断为 RR-TB 的所有患者中的 33.2%和 16.6%。
确定导致 RR-TB 诊断的确切 rpoB 多态性有可能使相当一部分 RR-TB 患者纳入利福布汀治疗方案。需要进行一项评估这些选定患者中含利福布汀的结核病治疗方案疗效的随机对照试验，为政策改变提供所需的证据。
