GenoType^® MTBDRsl assay for resistance to second-line anti-tuberculosis drugs

Abstract

Background Genotype® MTBDR sl (MTBDR sl ) is a rapid DNA‐based test for detecting specific mutations associated with resistance to fluoroquinolones and second‐line injectable drugs (SLIDs) in Mycobacterium tuberculosis complex. MTBDR sl version 2.0 (released in 2015) identifies the mutations detected by version 1.0, as well as additional mutations. The test may be performed on a culture isolate or a patient specimen, which eliminates delays associated with culture. Version 1.0 requires a smear‐positive specimen, while version 2.0 may use a smear‐positive or ‐negative specimen. We performed this updated review as part of a World Health Organization process to develop updated guidelines for using MTBDR sl . Objectives To assess and compare the diagnostic accuracy of MTBDR sl for: 1. fluoroquinolone resistance, 2. SLID resistance, and 3. extensively drug‐resistant tuberculosis, indirectly on a M. tuberculosis isolate grown from culture or directly on a patient specimen. Participants were people with rifampicin‐resistant or multidrug‐resistant tuberculosis. The role of MTBDR sl would be as the initial test, replacing culture‐based drug susceptibility testing (DST), for detecting second‐line drug resistance. Search methods We searched the following databases without language restrictions up to 21 September 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE; Embase OVID; Science Citation Index Expanded, Conference Proceedings Citation Index‐Science, and BIOSIS Previews (all three from Web of Science); LILACS; and SCOPUS; registers for ongoing trials; and ProQuest Dissertations & Theses A&I. We reviewed references from included studies and contacted specialists in the field. Selection criteria We included cross‐sectional and case‐control studies that determined MTBDR sl accuracy against a defined reference standard (culture‐based DST, genetic sequencing, or both). Data collection and analysis Two review authors independently extracted data and assessed quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool. We synthesized data for versions 1.0 and 2.0 separately. We estimated MTBDR sl sensitivity and specificity for fluoroquinolone resistance, SLID resistance, and extensively drug‐resistant tuberculosis when the test was performed indirectly or directly (smear‐positive specimen for version 1.0, smear‐positive or ‐negative specimen for version 2.0). We explored the influence on accuracy estimates of individual drugs within a drug class and of different reference standards. We performed most analyses using a bivariate random‐effects model with culture‐based DST as reference ...

Evaluation of the BACTEC MGIT 960 SL DST Kit and the GenoType MTBDRsl Test for Detecting Extensively Drugresistant Tuberculosis Cases

“…In addition to higher sensitivity rate for KAN, our results were similar to those of Ignatyeva et al [16] and Huang et al [22] and to those Theron et al [19] highlighted in their review article. Resistance to KAN can occur with eis promoter gene regions other than rrs regions, which are commonly responsible for resistance to AG/CPs.…”

“…However, the sensitivity rate for OFL in our study was higher than those reported by Tukvadze et al [17] and Jin et al [18]. Our results were consistent with those of the meta-analysis study of Theron et al [19] in which performance of the GenoType MTBDRsl method was evaluated by analyzing 21 studies.…”

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…The GenoType MTBDRsl-v1.0 was the first commercially available test for XDR tuberculosis. A Cochrane systematic review 257 of published performance data found a pooled sensitivity compared with DST of 83·1% (95% CI 78·7-86·7) and a pooled specificity of 97·7% (94·3-99·1) when testing cultured bacteria for resistance to fluoroquinolones. The test maintained similar accuracy to that seen when testing cultured bacteria when used to test samples of smearpositive sputum, with a sensitivity of 85·1% (71·9-2·7) and specificity of 98·2% (96·8-99·0).…”

“…The test maintained similar accuracy to that seen when testing cultured bacteria when used to test samples of smearpositive sputum, with a sensitivity of 85·1% (71·9-2·7) and specificity of 98·2% (96·8-99·0). 257 When testing cultured isolates for resistance to second-line injectable drugs, pooled sensitivities were 87·9% (82·1-92·0) for amikacin, 66·9% (44·1-83·8) for kanamycin, and 79·5% (58·3-91·4) for capreomycin. Specificities were 99·5% (97·5-99·9) for amikacin, 98·6% (96·1-99·5) for kanamycin, and 95·8% (93·4-97·3) for capreomycin.…”

MTBDR plus and MTBDR sl Assays: Absence of Wild-Type Probe Hybridization and Implications for Detection of Drug-Resistant Tuberculosis

“…The line probe assay, MTBDRplus version 2 (v2) (Hain Lifescience, Nehren, Germany), detects INH and RIF resistance, and the MTBDRsl (Hain Lifescience, Nehren, Germany) is designed to detect FQ, SLID, and ethambutol resistance. However, the reported sensitivities of these assays remain less than ideal for INH and SLID (14)(15)(16).…”