| Title: | Drug-resistant tuberculosis on the Balkan Peninsula : determination of drug resistance mechanisms with Xpert MTB/XDR and whole-genome sequencing analysis |
|---|
| Authors: | ID Truden, Sara, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Sodja, Eva, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Žolnir-Dovč, Marija, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author) |
|---|
| Files: |  URL - Source URL, visit https://journals.asm.org/doi/epdf/10.1128/spectrum.02761-22
 PDF - Presentation file, download (247,68 KB)
MD5: ABAC2A988B6B6BBD67DDB0207A17139A
|
|---|
| Language: | English |
|---|
| Typology: | 1.01 - Original Scientific Article |
|---|
| Organization: |  UKPBAG - University Clinic of Respiratory and Allergic Diseases Golnik
|
|---|
| Abstract: | 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. |
|---|
| Keywords: | drug resistant tuberculosis, whole-genome sequencing analysis, molecular diagnostics, Xpert MTB/XDR |
|---|
| Geographic coverage: | Balkanski polotok; |
|---|
| Publication status: | Published |
|---|
| Publication version: | Version of Record |
|---|
| Submitted for review: | 20.07.2022 |
|---|
| Article acceptance date: | 12.02.2023 |
|---|
| Publication date: | 06.03.2023 |
|---|
| Publisher: | ASM Press |
|---|
| Year of publishing: | 2023 |
|---|
| Number of pages: | str. 1-9 |
|---|
| Numbering: | Vol. 11, iss. 2 |
|---|
| Source: | Microbiology spectrum |
|---|
| PID: | 20.500.12556/DiRROS-23059  |
|---|
| UDC: | 616-002 |
|---|
| ISSN on article: | 2165-0497 |
|---|
| DOI: | 10.1128/spectrum.02761-22 |
|---|
| COBISS.SI-ID: | 159507971 |
|---|
| Copyright: | © 2023 Truden et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. |
|---|
| Note: | Nasl. z nasl. zaslona;
Opis vira z dne 22. 7. 2023;
|
|---|
| Publication date in DiRROS: | 18.07.2025 |
|---|
| Views: | 557 |
|---|
| Downloads: | 274 |
|---|
| Metadata: |    |
|---|
|
:
|
Copy citation |
|---|
| | | | Share: |  |
|---|
Hover the mouse pointer over a document title to show the abstract or click
on the title to get all document metadata. |
