Evaluation of Xpert(®) MTB/XDR test for susceptibility testing of Mycobacterium tuberculosis to first and second-line drugs in Uganda

BACKGROUND: Drug-Resistant Tuberculosis (DR-TB) is one of the key challenges toward TB control. There is an urgent need for rapid and accurate drug susceptibility tests (DST) for the most commonly used 1(st) and 2(nd) line TB drugs. DESIGN AND METHODS: In a blinded, laboratory-based cross-sectional study, we set out to validate the performance of the Xpert(®) MTB/XDR test for DST of M. tuberculosis. Sputum samples or culture isolates collected between January 2020 and December 2021 from patients with rifampicin resistance −TB and/or with higher suspicion index for isoniazid (INH) resistance and/or 2(nd) line fluoroquinolones (FQ) and injectable agents (IAs) were tested using the Xpert(®) MTB/XDR test from 11/September 2021 to 26/May/2022. Diagnostic accuracy and factors for laboratory uptake of Xpert(®) MTB/XDR test were compared to MGIT960 and the Hain Genotype(®) MTBDRplus and MDRsl assays (LPA) as reference DST methods. RESULTS: A total of 100 stored sputum samples were included in this study. Of the samples tested using MGIT960, 65/99 (65.6%) were resistant to INH, 5/100 (5.0%) resistant to FQ and none were resistant to IAs. The sensitivity and specificity, n (%; 95%Confidence Interval, CI) of Xpert(®) MTB/XDR test for; INH were 58 (89.2; 79.1-95.5) and 30 (88.2; 72.5-96.6), FQ; 4 (80.0; 28.3-99.4) and 95 (100; 96.2-100), respectively. The specificity for AIs was 100 (100; 96.3- 100). Using LPA as a reference standard, a total of 52/98 (53.1%) were resistant to INH, 3/100 (3.0%) to FQ, and none to IA. The sensitivity and specificity, n (%; 95%CI) of Xpert(®) MTB/XDR test compared to LPA for; INH was 50 (96.1; 86.7-99.5) and 34 (74.0; 58.8-85.7) and FQ 3 (100; 29.2-100) and 96 (99.0; 94.3-99.9) respectively. The specificity of IAs was 96 (100; 96.2-100). The factors for laboratory uptake and roll-out included; no training needed for technicians with previous Xpert-ultra experience and one day for those without, recording and reporting needs were not different from those of Xpert ultra, the error rate was 4/100 (4%), no uninterpretable results reported, test turn-around-time was 1hr/45 minutes and workflow similar to that of the Xpert-ultra test. CONCLUSION: There is high sensitivity and specificity of Xpert(®) MTB/XDR test for isoniazid, fluoroquinolones, and Injectable agents. There are acceptable Xpert(®) MTB/XDR test attributes for test uptake and roll-out.