The diagnostic accuracy of the GenoType^®MTBDRslassay for the detection of resistance to second-line anti-tuberculosis drugs

Abstract

Background Accurate and rapid tests for tuberculosis (TB) drug resistance are critical for improving patient care and decreasing the transmission of drug-resistant TB. Genotype®MTBDR sl (MTBDR sl ) is the only commercially-available molecular test for detecting resistance in TB to the fluoroquinolones (FQs; ofloxacin, moxifloxacin and levofloxacin) and the second-line injectable drugs (SLIDs; amikacin, kanamycin and capreomycin), which are used to treat patients with multidrug-resistant (MDR-)TB. Objectives To obtain summary estimates of the diagnostic accuracy ofMTBDR sl for FQ resistance, SLID resistance and extensively drug-resistant TB (XDR-TB; defined asMDR-TB plus resistance to a FQand a SLID) when performed (1) indirectly (ie on culture isolates confirmed as TB positive) and (2) directly (ie on smear-positive sputum specimens). To compare summary estimates of the diagnostic accuracy of MTBDR sl for FQ resistance, SLID resistance and XDR-TB by type of testing (indirect versus direct testing). The populations of interest were adults with drug-susceptible TB or drug-resistant TB. The settings of interest were intermediate and central laboratories. Search methods We searched the following databases without any language restriction up to 30 January 2014: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web of Knowledge; MEDION; LILACS; BIOSIS; SCOPUS; the metaRegister of Controlled Trials; the search portal of the World Health Organization International Clinical Trials Registry Platform; and ProQuest Dissertations & Theses A&I. Selection criteria We included all studies that determined MTBDR sl accuracy against a defined reference standard (culture-based drug susceptibility testing (DST), genetic testing or both).We included cross-sectional and diagnostic case-control studies.We excluded unpublished data and conference proceedings. Data collection and analysis For each study, two review authors independently extracted data using a standardized form and assessed study quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We performed meta-analyses to estimate the pooled sensitivity and specificity of MTBDR sl for FQ resistance, SLID resistance, and XDR-TB. We explored the influence of different reference standards. We performed the majority of analyses using a bivariate random-effects model against culture-based DST as the reference standard. Main results We included 21 unique studies: 14 studies reported the accuracy of MTBDR sl when done directly, five studies when done indirectly and two studies that did both. Of the 21 studies, 15 studies (71%) were cross-sectional and 11 studies ...

Performance of the New Version (v2.0) of the GenoType MTBDR sl Test for Detection of Resistance to Second-Line Drugs in Multidrug-Resistant Mycobacterium tuberculosis Complex Strains

“…The performance of MTBDRsl v1 (Table 3) was concordant with results of recent meta-analyses (11,19) as well as with our previous evaluation (15). These results confirm that v1 has high sensitivity and specificity for the detection of resistance to FQ, …”

Genomic Analysis of the Evolution of Fluoroquinolone Resistance in Mycobacterium tuberculosis Prior to Tuberculosis Diagnosis

“…The specificity of molecular diagnostic methods is high; the presence of any of a small number of mutations in the QRDR of gyrA (codons 94, 90, 91, 89, and 88) is strongly associated with FQ resistance. However, the sensitivity of these assays is approximately 80% (34), possibly due to their limited ability to detect resistant subpopulations. Even direct Sanger sequencing of PCR-amplified resistance loci requires minor alleles to be present at greater than 10 to 15% of the population (35).…”

Diagnostics for pulmonary tuberculosis

“…The performance for second-line DST is not as good as for rifampin, with the MTBDRsl only able to identify 85% of fluoroquinolone resistance and ranging from 66% to 87% for the injectables (amikacin, capreomycin and kanamycin). Still its specificity was good at >95% 59. In HIV-infected individuals there are little data, with one study of 90 patients with TB showing reduced sensitivity for fluoroquinolone resistance of 55.6% and as low as 9.4% for kanamycin resistance 60…”