LiquidArray^® MTB-XDR VER 1.0

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis or a closely related species and affecting over 10 million people worldwide. TB requires multidrug therapy over several months, which can fail due to mutations that result in drug resistance. Drug resistance accounted for over 400,000 estimated cases in 2020. Emergence and global spread of drug-resistant TB is a major medical and public health problem. Therefore, rapid and reliable detection of resistance-mediating mutations is essential for fast intervention and effective disease management at individual and public health level.

Drug resistance in TB is most commonly associated with first-line antibiotics, isoniazid and rifampicin, and requires tailored treatment with second-line anti-TB drugs, such as fluoroquinolones, bedaquiline and linezolid. Additional resistance to fluoroquinolones and at least one other of these “Group A” drugs leads to extensively drug-resistant (XDR-)TB, which is notoriously difficult to treat, using drugs with serious side effects over lengthy therapy. Closely monitoring drug-resistant strains equips doctors with information necessary to ensure most effective therapy and increase the chances of success for every TB patient.

LiquidArray^® MTB-XDR VER 1.0 offers reliable reporting of resistances to the 5 WHO-endorsed drugs: fluoroquinolones (moxifloxacin and levofloxacin), linezolid, amikacin and ethambutol, from sputum or culture specimens. In a single well, the test allows detection of M. tuberculosis complex as well as up to 28 mutations in resistance-mediating gyrA, gyrB, rplC, rrl, rrs and embB genes, according to latest WHO findings. The molecular genetic assay is powered by the innovative LiquidArray^® technology, providing next generation multiplexing in a familiar PCR format. Moreover, the results at a glance provide information on individual mutations, including differentiation between high-level and low-level resistance to moxifloxacin, allowing for instances of high-dose moxifloxacin treatment where low-level resistance is detected. Additionally, this feature alerts to instances where the certainty of resistance is currently not completely established but may do so in the future as more clinical and scientific data becomes available. The wealth of information generated in a single PCR reaction by LiquidArray^® MTB-XDR makes the assay an invaluable tool in guiding the doctors to choosing the most relevant individual therapy.

LiquidArray^® MTB-XDR VER 1.0 assay complements FluoroType^® MTBDR VER 2.0, which reports resistances to rifampicin and isoniazid. FluoroType^® MTBDR VER 2.0 is endorsed by the WHO as a test for the detection of pulmonary TB, and of rifampicin and isoniazid resistance, in people with signs and symptoms of pulmonary TB. The two assays can be run independently or, alternatively, in parallel or step-wise from the same DNA extraction. The possibility of reflex-testing from a single sample eliminates the necessity for a second patient sample, providing an efficient and time-saving diagnostic workflow for MDR- and XDR-TB from one sample. Starting with DNA extraction from decontaminated sputum or culture samples, and following PCR set-up, amplification and detection are performed with the FluoroCycler^® XT. The FluoroSoftware^® XT-IVD generates results at a glance, in an easy-to-use, easy-to-interpret test report. The streamlined workflow allows detection of resistance-conferring mutations in just 3 to 5.5 hours, depending on the number of samples, making the LiquidArray^® MTB-XDR VER 1.0 assay an indispensable tool for the rapid diagnosis of XDR-TB.

Starting from decontaminated sputum or culture samples, DNA can be extracted manually using the FluoroLyse kit and PCR set up in a few simple steps. Alternatively, automated DNA extraction and PCR setup is performed on the GenoXtract^® fleXT (12-96 samples). The choice of manual or automated extraction and PCR setup allows for a flexible workflow suitable for laboratories of any size.

The same DNA extract can be used for all mycobacteria assays that are based on LiquidArray^® technology, provided that the sample material is validated for the selected assays. Whether run in parallel or in a reflex-testing based approach, the streamlined workflow saves time and the necessity for additional patient samples.

Our three LiquidArray^®-based assays, FluoroType^® MTBDR VER 2.0, FluoroType^® Mycobacteria VER 1.0, and LiquidArray^® MTB-XDR VER 1.0, provide the broadest coverage in mycobacteria diagnostics: MTBC detection, first- and second-line resistances and over 30 NTMs. Following PCR set-up, LiquidArray^® amplification and detection are performed with the FluoroCycler^® XT, and the integrated FluoroSoftware^® XT-IVD software provides results at a glance in an easy-to-use easy-to-interpret test report.