Abstract
INTRODUCTION: Early detection of drug resistance in patients with tuberculosis (TB) is crucial for prompt and effective treatment. This study evaluated the performance of Xpert MTB/XDR assay (Xpert XDR) for detecting resistance to isoniazid (INH), fluoroquinolones (FLQ), aminoglycosides (AMG), and ethionamide (ETH) in patients with pulmonary TB (PTB) in Bangladesh. METHODS: Xpert XDR was performed on sputum samples from 793 Xpert MTB/RIF positive patients with PTB enrolled between April 2021 and March 2023. Results were compared with phenotypic drug susceptibility test (pDST) performed on Lowenstein-Jensen (L-J) media for the detection of resistance to INH, FLQ, AMG, and ETH. The performance of the assay was also compared between newly diagnosed or rifampicin (RIF)-sensitive versus re-treated or RIF-resistant patients with PTB. RESULTS: Of 793 samples tested by Xpert XDR, indeterminate results for INH, FLQ, AMG, and ETH were observed for 3 (0.4%), 5 (0.6%), 33 (4.2%), and 0 (0%) isolates, respectively. The assay's sensitivity and specificity compared to pDST was 94.0% (95% CI 90.5-96.4; 264/281) and 97.3% (95% CI 95.4-98.5; 495/509), respectively for INH; 86.0% (95% CI 78.2-91.8; 98/114) and 99.3% (95% CI 98.3-99.3; 669/674), respectively for FLQ; 85.7% (95% CI 42.1-99.6; 6/7) and 99.9% (95% CI 99.3-100.0; 752/753), respectively for AMG; and 25.0% (95% CI 19.0-31.7; 48/192) and 96.7% (95% CI 94.9-98.0; 581/601), respectively for ETH. Agreement of Xpert XDR with pDST was almost perfect for detecting resistance to INH, FLQ, and AMG (kappa: 0.91, 0.89, and 0.86, respectively), but fair for ETH (kappa: 0.28). Xpert XDR performed significantly better among re-treated or RIF-resistant patients with TB compared to newly diagnosed or RIF-sensitive cases. CONCLUSIONS: Given the high performance, Xpert XDR assay can be programmatically implemented nationwide for rapid and accurate detection of resistance to INH, FLQ, and AMG in patients with PTB, aiding clinicians in selecting appropriate regimens for the treatment of drug-resistant TB.