Evaluation of the GenoType (R) MTBDRsl assay for susceptibility testing of second-line anti-tuberculosis drugs

Abstract

BACKGROUND: The GenoType® MTBDRsl assay (Hains, Lifesciences, Germany) is a new rapid assay for detection of resistance to second-line anti-tuberculosis drugs. METHOD: The MTBDRsl assay was evaluated on 342 MDR-TB isolates for ofloxacin (OFX), kanamycin (KAN), capreomycin (CAP) and ethambutol (EMB) resistance and results were compared to the agar proportion method. Discrepant results were tested by DNA sequencing. RESULT: The sensitivity and specificity of MTBDRsl assay was 70.3% and 97.7% for OFX, 25.0% and 98.7% for KAN, 21.2% and 98.7% for CAP and 56.3% and 56.0% for EMB, respectively. DNA sequencing identified mutation that were not detected by MTBDRsl assay including: 8/11 phenotypically OFX-resistant isolates had mutation in gyrA (2/8 had additional mutation in the gyrB gene), 1/11 had mutation only in the gyrB gene; 6/21 phenotypically KAN-resistant isolate had mutation in rrs gene; 7/26 and 20/26 phenotypically CAP-resistant isolates had mutation in the rrs and tlyA genes, respectively. CONCLUSION: The MTBDRsl assay showed a lower sensitivity as compared to previous studies. The assay performed favourably for OFX; however the assay was less sensitive for detection of KAN/CAP resistance and demonstrated low sensitivity and specificity for EMB resistance. It is recommended that the MTBDRsl assay should include additional genes to achieve a better sensitivity for all the drugs tested.