Rifampicin-Monoresistant Tuberculosis Is Not the Same as Multidrug-Resistant Tuberculosis: a Descriptive Study from Khayelitsha, South Africa.
Rifampicin-Monoresistant Tuberculosis Is Not the Same as Multidrug-Resistant Tuberculosis: a Descriptive Study from Khayelitsha, South Africa.
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利福平单一耐药结核病与耐多药结核病不同：来自南非Khayelitsha的描述性研究
DOI：
10.1128/aac.00364-21
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发表时间：
2021-10-18
影响因子：
4.9
通讯作者：
Cox H
中科院分区：
文献类型：
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作者：
Salaam-Dreyer Z;Streicher EM;Sirgel FA;Menardo F;Borrell S;Reinhard M;Doetsch A;Cudahy PGT;Mohr-Holland E;Daniels J;Dippenaar A;Nicol MP;Gagneux S;Warren RM;Cox H
在南非，利福平单药耐药（RMR；利福平耐药和异烟肼敏感性）占所有利福平耐药结核病（RR-TB）的38%，并且正在增加。我们的目的是在高结核病、高耐药结核病和高艾滋病毒负担的背景下比较耐药结核病和耐多药结核病（MDR-TB）。使用2008年至2017年患者水平的临床数据和存储的RR结核分枝杆菌分离株以及现有的全基因组测序（WGS）数据来描述与RMR-TB相关的危险因素，并比较RMR-TB和MDR-TB之间的RR赋予突变。一组具有特定rr突变的分离株进行了半定量利福平表型药敏试验。在2,041例常规诊断的RR-TB患者中，463例（22.7%）患有RMR-TB。2013 - 2017年与2008 - 2012年相比，hiv阳性个体（调整优势比[aOR]， 1.4； 95%可信区间[CI]， 1.1 - 1.9）和诊断与RMR-TB相关（aOR, 1.3; 95% CI, 1.1 - 1.7）。在1119例（54.8%）有可用WGS数据显示RR-TB的患者中，观察到RMR和MDR分离株之间rpoB rr -授予突变分布的显著差异。与高水平RR相关的突变在MDR分离株中更为常见（在RMR分离株中，811/889[90.2%]比162/230 [70.4%],P < 0.0001）。特别是，rpoB L430P突变，赋予低水平RR，在32/230 (13.9%)RMR分离株中鉴定出，而在MDR分离株中鉴定出10/889 (1.1%)（P < 0.0001）。在临界浓度为0.5 μg/ml （0.125 ~ 1 μg/ml）时，10株rpoB L430P突变株中有7株表型易感。大多数（215/230 [93.5%]）RMR分离株显示对所有其他结核病药物敏感，突出了WGS在简化治疗方面的潜在益处。这些数据表明，耐药结核病的演变不同于耐多药结核病，可能与HIV感染有关。
Rifampin monoresistance (RMR; rifampin resistance and isoniazid susceptibility) accounts for 38% of all rifampin-resistant tuberculosis (RR-TB) in South Africa and is increasing. We aimed to compare RMR-TB with multidrug-resistant TB (MDR-TB) in a setting with high TB, RR-TB, and HIV burdens. Patient-level clinical data and stored RR Mycobacterium tuberculosis isolates from 2008 to 2017 with available whole-genome sequencing (WGS) data were used to describe risk factors associated with RMR-TB and to compare RR-conferring mutations between RMR-TB and MDR-TB. A subset of isolates with particular RR-conferring mutations were subjected to semiquantitative rifampin phenotypic drug susceptibility testing. Among 2,041 routinely diagnosed RR-TB patients, 463 (22.7%) had RMR-TB. HIV-positive individuals (adjusted odds ratio [aOR], 1.4; 95% confidence interval [CI], 1.1 to 1.9) and diagnosis between 2013 and 2017 versus between 2008 and 2012 (aOR, 1.3; 95% CI, 1.1 to 1.7) were associated with RMR-TB. Among 1,119 (54.8%) patients with available WGS data showing RR-TB, significant differences in the distribution of rpoB RR-conferring mutations between RMR and MDR isolates were observed. Mutations associated with high-level RR were more commonly found among MDR isolates (811/889 [90.2%] versus 162/230 [70.4%] among RMR isolates; P < 0.0001). In particular, the rpoB L430P mutation, conferring low-level RR, was identified in 32/230 (13.9%) RMR isolates versus 10/889 (1.1%) in MDR isolates (P < 0.0001). Among 10 isolates with an rpoB L430P mutation, 7 were phenotypically susceptible using the critical concentration of 0.5 μg/ml (range, 0.125 to 1 μg/ml). The majority (215/230 [93.5%]) of RMR isolates showed susceptibility to all other TB drugs, highlighting the potential benefits of WGS for simplified treatment. These data suggest that the evolution of RMR-TB differs from MDR-TB with a potential contribution from HIV infection.