Diagnostic performance of Xpert-based assays for spinal tuberculosis: a systematic review and diagnostic accuracy meta-analysis

Background Spinal tuberculosis is a severe form of extrapulmonary tuberculosis that often results in delayed diagnosis and irreversible neurological complications. Xpert MTB/RIF and Xpert MTB/RIF Ultra have been developed as rapid molecular diagnostic tools; however, their diagnostic performance in spinal tuberculosis remains uncertain, particularly across different reference standards. Objective To systematically evaluate the diagnostic accuracy of Xpert-based assays for spinal tuberculosis and assess the influence of different reference standards on pooled diagnostic estimates. Methods A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was performed from database inception to June 2026. Studies evaluating Xpert MTB/RIF or Xpert MTB/RIF Ultra in patients with suspected spinal tuberculosis and providing sufficient data to construct 2×2 diagnostic tables were included. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios were estimated using a bivariate random-effects model. Hierarchical summary receiver operating characteristic (HSROC) curves were generated. The primary analysis included studies using composite or clinical reference standards, whereas mycobacterial culture alone was evaluated in a separate sensitivity analysis. Results Twelve studies were included in the quantitative synthesis. In the primary analysis based on composite or clinical reference standards, the pooled sensitivity and specificity of Xpert-based assays were 0.77 (95% CI: 0.66–0.86) and 1.00 (95% CI: 0.99–1.00), respectively. The pooled positive and negative likelihood ratios were 43.86 (95% CI: 23.65–81.36) and 0.24 (95% CI: 0.15–0.37), respectively, with a diagnostic odds ratio of 213.28 (95% CI: 89.30–509.42). In the sensitivity analysis using mycobacterial culture as the reference standard, pooled sensitivity increased to 0.94 (95% CI: 0.88–0.98), whereas specificity decreased to 0.62 (95% CI: 0.44–0.78). Only one included study evaluated Xpert MTB/RIF Ultra, limiting conclusions regarding its comparative performance. Conclusion Xpert-based assays demonstrate high diagnostic accuracy for spinal tuberculosis, particularly strong confirmatory capability due to high specificity. However, negative results alone are insufficient to exclude disease. The choice of reference standard substantially influences pooled diagnostic estimates, highlighting the importance of interpreting Xpert results together with clinical, radiological, microbiological, and histopathological findings. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261427181 , identifier CRD420261427181.