BACKGROUND We evaluated the performance of pyrosequencing, a genotypic test which detects TB and XDR-defining mutations within 6 h, directly on CSF samples for diagnosing TB meningitis(TBM). METHODS This retrospective, diagnostic accuracy study was conducted in Hinduja hospital, Mumbai from May-2017 to May-2019. 107 consecutive patients with physician-suspected TBM for whom CSF pyrosequencing was requested were screened. Seven patients with incomplete data were excluded. Diagnostic accuracy of pyrosequencing was compared with Xpert MTB/Rif and TBMGIT (TB Mycobacterial Growth Indicator Tube) culture against the uniform case definition of definite or probable TBM. Susceptibility concordance rate of pyrosequencing with TBMGIT culture and Xpert MTB/Rif was determined. RESULTS The study cohort comprised of 100 patients[Definite(n = 33), Probable(n = 20), Possible(n = 30), Alternative(n = 17)] with 50% males[median age(years):38(Range:2-87)]. Against the uniform case definition, pyrosequencing had 98·11%(95%CI 89·93-99·95; n = 52/53) sensitivity and 97·79%(86·31-99·67; n = 44/45) negative predictive value(NPV) compared with 43.39%(29·83-57·72; n = 23/53,p < 0.0001) sensitivity and 61.04%(55·31-66·48; n = 47/77) NPV for Xpert MTB/Rif and 45·28%(31·56-59·55; n = 24/53,p < 0.0001) sensitivity and 61·84%(55·92-67·43; n = 47/76) NPV for TBMGIT culture. Susceptibility concordance rate of pyrosequencing with phenotypic Drug Susceptibility Testing was 91.3%(n = 21/23) and with Xpert MTB/Rif was 95·45%(n = 21/22). CONCLUSION CSF pyrosequencing is significantly more sensitive than Xpert MTB/Rif and TBMGIT culture for diagnosing TBM. Additionally, it facilitates early therapeutic decision-making by providing information on XDR-defining mutations.

中文翻译：

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脑脊液焦磷酸测序诊断结核性脑膜炎的评价：一项回顾性诊断准确性研究

背景 我们评估了焦磷酸测序的性能，这是一种基因型测试，可在 6 小时内检测 TB 和 XDR 定义突变，直接在 CSF 样本上用于诊断结核病脑膜炎 (TBM)。方法 这项回顾性的诊断准确性研究于 2017 年 5 月至 2019 年 5 月在孟买的印度教医院进行。对 107 名医生怀疑为 TBM 且要求进行 CSF 焦磷酸测序的连续患者进行了筛选。7 名数据不完整的患者被排除在外。将焦磷酸测序的诊断准确性与 Xpert MTB/Rif 和 TBMGIT（结核分枝杆菌生长指示管）培养物与确定或可能的 TBM 的统一病例定义进行比较。确定焦磷酸测序与 TBMGIT 培养和 Xpert MTB/Rif 的敏感性一致率。结果 研究队列由 100 名患者组成[确定（n = 33），可能（n = 20），可能（n = 30），替代（n = 17）] 50% 男性[中位年龄（年）：38（范围：2-87）]。与统一的病例定义相反，焦磷酸测序的灵敏度为 98·11%（95%CI 89·93-99·95；n = 52/53）和 97·79%（86·31-99·67；n = 44/45） ) 阴性预测值 (NPV) 与 43.39% (29·83-57·72; n = 23/53,p < 0.0001) 敏感性和 61.04% (55·31-66·48; n = 47/77) NPV 相比对于 Xpert MTB/Rif 和 45·28%（31·56-59·55；n = 24/53，p < 0.0001）灵敏度和 61·84%（55·92-67·43；n = 47/76） TBMGIT 文化的 NPV。焦磷酸测序与表型药物敏感性测试的敏感性一致率为 91.3%（n = 21/23），与 Xpert MTB/Rif 的敏感性一致率为 95·45%（n = 21/22）。结论 在诊断 TBM 方面，CSF 焦磷酸测序比 Xpert MTB/Rif 和 TBMGIT 培养更敏感。此外，