Diagnosis of rifampicin-resistant tuberculosis: Discordant results by diagnostic methods

Abstract

The performance of the Xpert© MTB/RIF and MTBDRplus assays for the detection of rifampicin resistant Mycobacterium tuberculosis was compared to culture-based drug susceptibility testing in 30 specimens with rifampicin-resistant and rifampicin-indeterminate Xpert MTB/RIF results collected between March 2012 and March 2014. Xpert MTB/RIF and MTBDRplus were 100% sensitive and 100% concordant for rifampicin resistance detection, but 3 of 13 samples (23%) positive for rifampicin resistance on Xpert MTB/RIF and MTBDRplus were negative for rifampicin resistance on mycobacteria growth indicator tube drug susceptibility testing. Specificity was 72% for Xpert MTB/RIF and 80% for MTBDRplus. Positive predictive value for Xpert MTB/RIF for multidrug resistant tuberculosis was 47.8% for new patients and 77.8% for previously treated patients; negative predictive value was 100% for both new and previously treated patients. The discordant rifampicin resistance test results indicate a need to fully characterise circulating rifampicin resistant Mycobacterium tuberculosis strains in Zambia and to inform the development of guidelines for decision-making in relation to diagnosis of drug-resistant tuberculosis.

Discordance of the Repeat GeneXpert MTB/RIF test for Rifampicin Resistance Detection among Patients Initiating MDR-TB Treatment in Uganda

“…In Uganda the testing strategy is to use Xpert as the frontline test for TB diagnosis and detection of RR. The high discordance of repeat Xpert for RR has been documented in previous studies 11,13 . The GLI guidelines recommends repeat Xpert testing for patients with a low pretest probability of RR such as the new TB cases 14 .…”

Discordant line probe genotypic testing vs culture-based drug susceptibility phenotypic testing in TB endemic KwaZulu-Natal: Impact on bedside clinical decision making

“…When rapid molecular tests are negative but clinical judgment and suspicion for MDR-TB is high, then MDR-TB treatment should continue until the phenotypic susceptibility results become available. The question of repeat testing using a different platform has also been suggested for initial laboratory results on specimens that are RIF sensitive and INH resistant [13] , [50] . Conversely if an initial result is positive for RIF resistance and there is no clinical suspicion of DR-B, the result should be treated with reserve [51] , [52] .…”

“…The gold-standard of diagnosis, solid culture-based drug susceptibility testing (DST), provides results in 4–6 weeks, whereas liquid culture-based DST takes approximately 2 weeks [9] .As per WHO recommendations, many laboratories use additional phenotypic methods to confirm the molecular drug susceptibility results and to also test susceptibility to second and third line anti-TB drugs [10] , [11] , [12] . This concurrent dual use of testing platforms has created an emergence of discordant results for rifampicin (RIF) and isoniazid (INH) testing on the same patient sample produced from different platforms, resulting in a diagnostic dilemma for attending clinicians [13] .…”

Rifampicin susceptibility discordance between Xpert MTB/RIF G4 and Xpert Ultra before MDRT-TB treatment initiation: A case report from Uganda

“…In our case, with access to other standard facilities such as the Uganda NTRL for results comparison, it took ∼20 days (from 15th August to 03rd September 2019) to resolve discordance. Ultra has been found to unambiguously identify a wide range of RRDR mutations [9] , referred to as “disputed mutations” which had been reported to be missed by the pDST [10] , [11] , [12] , but none have been reported between two versions of GeneXpert assays currently in use. This is because the nature of the discordance is different, Xpert detects disputed mutations which are missed by the phenotypic drug susceptibility testing.…”