Central TB Reference Laboratory, Dar es Salaam, Tanzania.
Muhimbili Research Centre, National Institute for Medical Research, Dar es Salaam, Tanzania.
BMC Infect Dis. 2024 Jul 4;24(1):672. doi: 10.1186/s12879-024-09562-z.
Early diagnosis of tuberculosis (TB) and universal access to drug-susceptibility testing (DST) are critical elements of the WHO End TB Strategy. Current rapid tests (e.g., Xpert MTB/RIF and Ultra-assays) can detect rifampicin resistance-conferring mutations, but cannot detect resistance to Isoniazid and second-line anti-TB agents. Although Line Probe Assay is capable of detecting resistance to second-line anti-TB agents, it requires sophisticated laboratory infrastructure and advanced skills which are often not readily available in settings replete with TB. A rapid test capable of detecting Isoniazid and second-line anti-TB drug resistance is highly needed.
We conducted a diagnostic accuracy study to evaluate a new automated Xpert MTB/XDR 10-colour assay for rapid detection of Isoniazid and second-line drugs, including ethionamide, fluoroquinolones, and injectable drugs (Amikacin, Kanamycin, and Capreomycin). Positive Xpert MTB/RIF respiratory specimens were prospectively collected through routine diagnosis and surveillance of drug resistance at the Central TB Reference Laboratory in Tanzania. Specimens were tested by both Xpert XDR assay and LPA against culture-based phenotypic DST as the reference standard.
We analysed specimens from 151 TB patients with a mean age (SD) of 36.2 (12.7) years. The majority (n = 109, 72.2%) were males. The sensitivity for Xpert MTB/XDR was 93.5% (95% CI, 87.4-96.7); for Isoniazid, 96.6 (95% CI, 92.1-98.6); for Fluoroquinolone, 98.7% (95% Cl 94.8-99.7); for Amikacin, 96.6%; and (95% CI 92.1-98.6) for Ethionamide. Ethionamide had the lowest specificity of 50% and the highest was 100% for Fluoroquinolone. The diagnostic performance was generally comparable to that of LPA with slight variations between the two assays. The non-determinate rate (i.e., invalid M. tuberculosis complex detection) of Xpert MTB/XDR was 2·96%.
The Xpert MTB/XDR demonstrated high sensitivity and specificity for detecting resistance to Isoniazid, Fluoroquinolones, and injectable agents. This assay can be used in clinical settings to facilitate rapid diagnosis of mono-isoniazid and extensively drug-resistant TB.
结核病（TB）的早期诊断和普遍获得药敏检测（DST）是世卫组织终止结核战略的关键要素。目前的快速检测（例如 Xpert MTB/RIF 和 Ultra 检测）可检测利福平耐药相关突变，但无法检测异烟肼和二线抗结核药物的耐药性。虽然线探针检测（LPA）能够检测二线抗结核药物的耐药性，但它需要复杂的实验室基础设施和高级技能，而这些在充满结核病的环境中往往无法轻易获得。因此，非常需要一种能够检测异烟肼和二线抗结核药物耐药性的快速检测方法。
我们进行了一项诊断准确性研究，以评估一种新的自动化 Xpert MTB/XDR 10 色检测方法，用于快速检测异烟肼和二线药物，包括乙胺丁醇、氟喹诺酮类药物和注射用药物（阿米卡星、卡那霉素和卷曲霉素）。通过在坦桑尼亚中央结核病参考实验室进行常规诊断和耐药监测，前瞻性收集了 Xpert MTB/RIF 呼吸道标本。将这些标本分别用 Xpert XDR 检测法和 LPA 进行检测，以培养为基础的表型药敏检测（DST）作为参考标准。
我们分析了 151 名结核病患者的标本，他们的平均年龄（标准差）为 36.2（12.7）岁。大多数患者（n=109，72.2%）为男性。Xpert MTB/XDR 的敏感性为 93.5%（95%CI，87.4-96.7）；异烟肼为 96.6%（95%CI，92.1-98.6）；氟喹诺酮类药物为 98.7%（95%CI，94.8-99.7）；阿米卡星为 96.6%（95%CI，92.1-98.6）；乙胺丁醇为 50%。氟喹诺酮类药物的特异性最高，为 100%；乙胺丁醇的特异性最低，为 50%。与 LPA 相比，该检测方法的诊断性能大致相当，两种检测方法之间略有差异。Xpert MTB/XDR 的不确定率（即结核分枝杆菌复合体检测无效）为 2.96%。
Xpert MTB/XDR 对检测异烟肼、氟喹诺酮类药物和注射用药物的耐药性具有较高的敏感性和特异性。该检测方法可用于临床环境，以促进对单异烟肼和广泛耐药结核的快速诊断。
