Performance evaluation of the Xpert MTB/XDR test for the detection of drug resistance toMycobacterium tuberculosisamong people diagnosed with tuberculosis in South Africa

Background: Tuberculosis (TB) remains a significant public health concern in South Africa, with high incidence rates and a growing burden of drug-resistant TB. This study aimed to assess the diagnostic performance of the Xpert MTB/XDR test, a novel molecular assay, for detecting drug resistance in TB patients using archived sputum sediments. Methods: The study involved a comprehensive analysis of 322 samples collected from presumptive TB patients between 2016 - 2019 across South Africa, previously characterized by phenotypic and genotypic methods. The Xpert MTB/XDR test was evaluated for its ability to detect resistance to isoniazid (INH), ethionamide (ETH), fluoroquinolones (FLQ), and second-line injectable drugs (SLID) compared to phenotypic drug susceptibility testing (pDST) and whole-genome sequencing (WGS). The Xpert MTB/RIF Ultra and G4 tests were performed to determine agreement with this test for TB detection. Findings: The Xpert MTB/XDR test performance showed excellent sensitivity and specificity for detecting Mycobacterium tuberculosis ( M. tuberculosis ), with a sensitivity of 98.3% and specificity of 100% compared to culture. The sensitivities using a composite reference standard, pDST and sequencing, were over 90% for INH, FLQ, AMK, KAN, and CAP resistance, meeting the WHO target product profile criteria for this class. A lower sensitivity of 65.9% for ETH resistance was observed, driven by the limited targets covered by the assay. Interpretation: The Xpert MTB/XDR test offers a promising solution for the rapid detection of drug-resistant TB in South Africa. It could significantly enhance TB control efforts in this setting and contribute to improved patient care and management.