Background
Genotype® MTBDR
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(MTBDR
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) 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
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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
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.
Objectives
To assess and compare the diagnostic accuracy of MTBDR
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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
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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
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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
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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 ...