Department of Laboratory Medicine,West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Clin Infect Dis. 2011 Dec;53(11):1067-73. doi: 10.1093/cid/cir663. Epub 2011 Oct 21.
Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis and causes high mortality and morbidity. Isoniazid resistance is strongly predictive of death in patients with TBM.
In the present study, using polymerase chain reaction (PCR) and Genotype MTBDRplus line-probe assay, we investigated the drug resistance in patients with TBM living in Southwest China.
Our results showed that only one-third of patients with TBM had a positive result for Mycobacterium tuberculosis culture from cerebrospinal fluid (CSF). PCR-based detection of M. tuberculosis DNA in CSF is not only an alternative diagnostic approach for TBM but also can be further used for the detection of drug resistance when combined with the MTBDRplus assay, the results of which were consistent with the classic drug susceptibility test. However, it further provided the molecular profile of the mutations can be conducted much faster than the classic drug susceptibility test can (1 day vs 30-40 days, respectively). In the studied 30 CSF samples from patients with TMB, we found a rate of 64.29% for isoniazid resistance, 39.29% for rifampicin resistance, and 32.14% for multidrug-resistant tuberculosis, which is relatively higher than the reported resistance in pulmonary tuberculosis. However, the molecular profile indicated that the most frequently observed mutations in the rpoB and katG genes are also responsible for drug resistance in TBM.
Our data suggest that the MTBDRplus line-probe assay is capable of detecting drug resistance for the CSF samples that have a PCR-positive result. We recommend PCR-based diagnosis and drug resistance test as routine assays for patients with suspected TBM.
结核性脑膜炎（TBM）是最严重的肺外结核病形式，可导致高死亡率和高发病率。异烟肼耐药性是 TBM 患者死亡的强烈预测因素。
在本研究中，我们使用聚合酶链反应（PCR）和基因型 MTBDRplus 线探针分析，调查了居住在中国西南部的 TBM 患者的耐药性。
我们的结果表明，只有三分之一的 TBM 患者的脑脊液（CSF）分枝杆菌培养呈阳性。CSF 中结核分枝杆菌 DNA 的基于 PCR 的检测不仅是 TBM 的替代诊断方法，而且当与 MTBDRplus 分析结合使用时，还可以进一步用于检测耐药性，其结果与经典药敏试验一致。然而，它进一步提供了突变的分子谱可以比经典药敏试验更快地进行（分别为 1 天和 30-40 天）。在研究的 30 例来自 TMB 患者的 CSF 样本中，我们发现异烟肼耐药率为 64.29%，利福平耐药率为 39.29%，耐多药结核病为 32.14%，相对高于报告的肺结核耐药率。然而，分子谱表明 rpoB 和 katG 基因中最常见的突变也与 TBM 的耐药性有关。
我们的数据表明，MTBDRplus 线探针分析能够检测具有 PCR 阳性结果的 CSF 样本中的耐药性。我们建议将基于 PCR 的诊断和耐药性测试作为疑似 TBM 患者的常规检测。
