Comparison of Quantamatrix Multiplexed Assay Platform and GenoType MTBDR Assay Using Smear-Positive Sputum Specimens From Patients With Multidrug- Resistant/Extensively Drug-Resistant Tuberculosis in South Korea

Abstract

Rapid detection of drug-resistant tuberculosis (DR-TB) is crucial for timely treatment and management. The GenoType MTBDR plus and MTBDR sl (MTBDR) assays have been endorsed by the World Health Organization (WHO) for the detection of DR-TB. However, MTBDR assays cannot simultaneously detect multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Furthermore, interpretation of the MTBDR assay requires trained people, and the assay has low sample throughput, processing only up to 12 samples in parallel. We have developed the Quantamatrix Multiplexed Assay Platform (QMAP) to detect MDR-/XDR-TB simultaneously. The interpretation of QMAP results is automated, and the platform can process up to 96 samples in parallel. To compare the performance of QMAP with MTBDR assays, we performed QMAP and the MTBDR assay on 76 smear-positive, Mycobacterium tuberculosis culture-positive sputum specimens. Compared with phenotypic drug susceptibility testing (DST) results, the sensitivity and specificity of QMAP were 100 and 98% for rifampin resistance, 80 and 100% for isoniazid resistance, 44.4 and 100% for ethambutol resistance, 100 and 100% for fluoroquinolone resistance, and 100 and 100% for second-line injectable drug resistance, respectively. The sensitivity and specificity of MTBDR assays were 100 and 98% for rifampin resistance, 80 and 100% for isoniazid resistance, 44.4 and 98.1% for ethambutol resistance, 100 and 100% for fluoroquinolone resistance, and 100 and 100% for second-line injectable drug resistance, respectively. The sensitivity and specificity of QMAP were 85.0 and 100%, respectively, for the detection of MDR-TB and 100 and 100%, respectively, for XDR-TB. The sensitivity and specificity of MTBDR assays was consistent with those of QMAP. Our study showed that the QMAP assay has sensitivity and specificity equivalent to that of MTBDR assays in smear-positive sputum specimens. In combination with phenotypic DST, QMAP might be useful as a supplementary DST assay for rapid detection of MDR-/XDR-TB.

Mutation and Transmission Profiles of Second-Line Drug Resistance in Clinical Isolates of Drug-Resistant Mycobacterium tuberculosis From Hebei Province, China

“…The traditional phenotypic DSTs lead serious delays to the detection of resistance just because of the extremely slow growth of M. tuberculosis . However, several commercial diagnostic tests such as GeneXpert MTB/RIF, Genotype MTBDRplus/MTBDRsl assays, have been developed to rapidly detect both first- and second-line drug resistance in M. tuberculosis by scanning the associated mutations (Xie et al, 2017; Kim et al, 2019). Our performance showed that analysis of the associated mutations was recommended to provide a good sensitivity for rapid verification of FQ r (79.4%), SLID r (50.8%), Pre-XDR (80.4%), and XDR (92.9%).…”

Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates—Chennai, India, 2013–2016

“…As the LPA kits were received at a subsidized cost, we are unable to perform a cost comparison among the molecular diagnostics in an ideal scenario. However, a recent study from South Korea analyzed the costs associated with various methodologies for DST ( Kim et al, 2019 ). A similar analysis of associated costs in India may inform policies related to the appropriate application of these methodologies for the detection of drug-resistance in clinical, programmatic and research settings.…”

Characterization of resistance mutations against first and second line antituberculosis drugs of multi-drug resistant Mycobacterium tuberculosis strains isolated from clinical samples by In house PCR method and comparison of resistance profiles

“…For these reasons, rapid molecular detection methods have become an important need in the definition of resistance 20 . Since the commercial molecular tests (Xpert MTB / RIF, GenoType MTBDR / MTB DRplus, sequence analysis) used for this purpose are expensive and require infrastructure, studies are continuing on fast, practical and inexpensive tests to identify resistance 21,22 .…”