20.500.12556/DiRROS-23059 Drug-resistant tuberculosis on the Balkan Peninsula determination of drug resistance mechanisms with Xpert MTB/XDR and whole-genome sequencing analysis Drug-resistant tuberculosis on the Balkan Peninsula: determination of drug resistance mechanisms with Xpert MTB/XDR and whole-genome sequencing analysis The new molecular assay Xpert MTB/XDR (Cepheid, Sunnyvale, CA, USA) was launched in 2021 to detect Mycobacterium tuberculosis (MT) complex with mutations conferring resistance to isoniazid (INH), ethionamide (ETH), fluoroquinolone (FQ), and second-line injectable drugs (SLIDs). The aim of our study was to evaluate the performance of the Xpert MTB/XDR rapid molecular assay on rifampicin-resistant, multidrug-resistant, and pre-extensively resistant tuberculosis (TB) isolates in a clinical laboratory in the Balkan Peninsula compared to a phenotypic drug susceptibility test (pDST). Xpert MTB/XDR was used to test positive Bactec MGIT 960 (Becton, Dickinson and Co., Franklin Lakes, NJ, USA) cultures or DNA isolates. In the case of discrepant results between Xpert MTB/XDR and pDST, the usefulness of whole-genome sequencing (WGS) was emphasized. In our study, 80 MT isolates from different Balkan countries were selectively chosen from the National Mycobacterial Strain Collection in Golnik, Slovenia. Isolates were tested with the Xpert MTB/XDR assay, conventional pDST, and WGS. Xpert MTB/XDR showed high sensitivities of 91.9%, 100%, and 100% for detecting INH, FQ, and SLID resistance, respectively, compared to pDST. In contrast, low sensitivity (51.9%) for ETH resistance was achieved because isolates harbored widespread mutations across the ethA gene. The specificity of Xpert MTB/XDR was 100% for all drugs except for INH (66.7%). Further investigation with WGS revealed −57c→t mutations in the oxyR-ahpC region marked with uncertain significance, which caused the low specificity for detecting INH resistance with the new assay. Xpert MTB/XDR can be used in clinical laboratories for the rapid detection of INH, FQ, and SLID resistance. Moreover, it can be used to rule in resistance to ETH. Additional use of WGS is recommended in cases of discrepant results between pDST and Xpert MTB/XDR. Future improvements of Xpert MTB/XDR with the inclusion of additional genes may increase the usefulness of the assay. drug resistant tuberculosis whole-genome sequencing analysis molecular diagnostics Xpert MTB/XDR proti zdravilom odporna tuberkuloza sekvenciranje celotnega genoma molekularna diagnostika Xpert MTB/XDR true false true ASM Press Microbiology spectrum Angleški jezik Slovenski jezik Balkanski polotok; © 2023 Truden et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Neznano 2025-07-18 14:26:38 2025-07-18 14:26:38 2025-10-24 03:53:02 0000-00-00 00:00:00 2023 0 0 Nasl. z nasl. zaslona; Opis vira z dne 22. 7. 2023; str. 1-9 iss. 2 Vol. 11 Mar./Apr. 2023 0000-00-00 Zaloznikova Objavljeno apc 2022-07-20 2023-02-12 2023-03-06 616-002 2165-0497 10.1128/spectrum.02761-22 159507971 https://journals.asm.org/doi/epdf/10.1128/spectrum.02761-22 1 74681b49-63d2-11f0-9bb7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=33800 RAZ_Truden_Sara_2023.pdf RAZ_Truden_Sara_2023.pdf 1 ABAC2A988B6B6BBD67DDB0207A17139A 7513adcc8fa406c87b2a44647e2cef8ab4a923043edaef55e5e408ee53544a4f 236bdbec-63d3-11f0-9bb7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=33801 Univerzitetna klinika za pljučne bolezni in alergijo Golnik 0 0 0