Evaluation Of Csf Pyrosequencing To Diagnose Tuberculous Meningitis: A Retrospective Diagnostic Accuracy Study

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.