Xpert MTB/XDR for detection of pulmonary tuberculosis and resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin

Abstract

Background The World Health Organization (WHO) End TB Strategy stresses universal access to drug susceptibility testing (DST). DST determines whether Mycobacterium tuberculosis bacteria are susceptible or resistant to drugs. Xpert MTB/XDR is a rapid nucleic acid amplification test for detection of tuberculosis and drug resistance in one test suitable for use in peripheral and intermediate level laboratories. In specimens where tuberculosis is detected by Xpert MTB/XDR, Xpert MTB/XDR can also detect resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin. Objectives To assess the diagnostic accuracy of Xpert MTB/XDR for pulmonary tuberculosis in people with presumptive pulmonary tuberculosis (having signs and symptoms suggestive of tuberculosis, including cough, fever, weight loss, night sweats). To assess the diagnostic accuracy of Xpert MTB/XDR for resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin in people with tuberculosis detected by Xpert MTB/XDR, irrespective of rifampicin resistance (whether or not rifampicin resistance status was known) and with known rifampicin resistance. Search methods We searched multiple databases to 23 September 2021. We limited searches to 2015 onwards as Xpert MTB/XDR was launched in 2020. Selection criteria Diagnostic accuracy studies using sputum in adults with presumptive or confirmed pulmonary tuberculosis. Reference standards were culture (pulmonary tuberculosis detection); phenotypic DST (pDST), genotypic DST (gDST),composite (pDST and gDST) (drug resistance detection). Data collection and analysis Two review authors independently reviewed reports for eligibility and extracted data using a standardized form. For multicentre studies, we anticipated variability in the type and frequency of mutations associated with resistance to a given drug at the different centres and considered each centre as an independent study cohort for quality assessment and analysis. We assessed methodological quality with QUADAS‐2, judging risk of bias separately for each target condition and reference standard. For pulmonary tuberculosis detection, owing to heterogeneity in participant characteristics and observed specificity estimates, we reported a range of sensitivity and specificity estimates and did not perform a meta‐analysis. For drug resistance detection, we performed meta‐analyses by reference standard using bivariate random‐effects models. Using GRADE, we assessed certainty of evidence of Xpert MTB/XDR accuracy for detection of resistance to isoniazid and fluoroquinolones in people irrespective of rifampicin resistance and to ethionamide and amikacin in people with known rifampicin resistance, reflecting real‐world situations. We used pDST, except for ethionamide resistance where we considered gDST a better reference standard. Main results W...

Evaluation of Xpert®MTB/XDR test for susceptibility testing ofMycobacterium tuberculosisto first and second-line drugs in Uganda

“…The test achieved acceptable attributes in terms of training needs, test Turn-Around Time (TAT), error rates as well as test workflow. The high sensitivity for both INH and FQs obtained in this study is in agreement with the previous validation studies including a Cochrane review[9][10][11]. The lower specificity of the Xpert ® MTB/XDR test in our study may be attributed to the study design which used the previously recorded results of the reference standard, and in some cases, M.…”

Rapid Diagnosis of XDR and Pre-XDR TB: A Systematic Review of Available Tools

“…Xpert MTB/XDR test is a rapid, automated NAAT test at low complexity. 21,22 It does not require any sophisticated laboratory infrastructure. The molecular amplification of small quantity of genetic materials takes place inside the cartridge and require less than 2 h to provide results.…”

“…12,18,19 Improving treatment success will require access to rapid diagnostic tests able to reliably detect and classify drug resistance, and inform clinicians designing individual regimens. 20 In 2021-2022 a Cochrane Review 21,22 investigated the efficacy of Xpert MTB/XDR to rapidly detect resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin (but not to the other injectable drugs kanamycin and capreomycin). However, no previous systematic reviews have comprehensively investigated the features of tests available to diagnose pre-XDR/XDR-TB.…”

Review on Bovine Tuberculosis: An Emerging Disease Associated with Multidrug-Resistant Mycobacterium Species

“…The authors recommended the use of PrimeStore ® Molecular Transport Medium, in combination with Xpert ® MTB/RIF Ultra assay (an automated cartridge-based semi-quantitative nested RT-PCR assay that detects DNA of MBTC and rifampicin (RIF) resistance in clinical specimens) as a safe and rapid PM screening test for M. bovis in buffaloes. In humans, Xpert MTB/RIF has recently become a significant breakthrough in TB diagnosis [ 122 ]. This test can detect MBTC DNA and mutations associated with antitubercular drug resistance.…”