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

The rapid test GenoType® MTBDRsl for testing resistance to second-line TB drugs

New Cochrane Review from EHCRC Partners in the Cochrane Database of Systematic Reviews

Cochrane Database of Systematic Reviews 2014, Issue 10. Art. No.: CD010705.

To read the full review please follow this link: DOI: 10.1002/14651858.CD010705.pub2. 

Theron G1, Peter J, Richardson M1, Barnard M3, Donegan S2, Warren R4, Steingart KR5, Dheda K6.

1 University of Cape Town, Department of Medicine, Cape Town, Western Cape, South Africa.
2 Liverpool School of Tropical Medicine, Department of Clinical Sciences, Liverpool, UK
3 Stellenbosch University, Task Laboratory, Dept of Biochemical Sciences, Faculty of Medicine & Health Sciences, Matieland, South Africa
4 Stellenbosch University, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Matieland, South Africa
5 Liverpool School of Tropical Medicine, Cochrane Infectious Diseases Group, Liverpool, UK
6 University of Cape Town, Division of Pulmonology, Department of Medicine, Cape Town, South Africa

Background
Different drugs are available to treat people with tuberculosis (TB), but resistance to these drugs is a growing problem. People with drug-resistant TB are more likely to die than people with drug-susceptible TB. People with drug-resistant TB require "second-line" TB drugs that, compared with "first-line" TB drugs used to treat drug-susceptible TB, cause more side effects and must be taken for longer. Extensively drug-resistant TB (XDR-TB) is a type of TB that is resistant to almost all TB drugs. A rapid and accurate test could identify people with drug-resistant TB, likely improve patient care, and reduce the spread of drug-resistant TB.

Test evaluated by this review
GenoType® MTBDRsl (MTBDRsl) is the only rapid test that detects resistance to second-line fluoroquinolone drugs and the second-line injectable drugs. The test also detects XDR-TB. MTBDRsl can be performed on TB bacteria grown by culture from sputum, which takes a long time (indirect testing), or immediately on sputum (direct testing).

Main results
We examined evidence available up to 30 January 2014 and included 21 studies, 11 of which were in low-income or middle-income countries.

What do these results mean?

Fluoroquinolone drugs
By indirect testing, the test detected 83% of people with fluoroquinolone resistance and rarely gave a positive result for people without resistance. In a population of 1000 people, where 170 have fluoroquinolone resistance, MTBDRsl will correctly identify 141 people with fluoroquinolone resistance and miss 29 people. In this same population of 1000 people, where 830 people do not have fluoroquinolone resistance, the test will correctly classify 811 people as not having fluoroquinolone resistance and misclassify 19 people as having resistance (moderate quality evidence).

By direct testing, the test detected 85% of people with fluoroquinolone resistance and rarely gave a positive result for people without resistance (moderate quality evidence).

Second-line injectable drugs
By indirect testing, the test detected 77% of people with second-line injectable drug resistance and rarely gave a positive result for people without resistance. In a population of 1000 people, where 230 have second-line injectable drug resistance, MTBDRsl will correctly identify 177 people with second-line injectable drug resistance and miss 53 people. In this same population of 1000 people, where 770 do not have second-line injectable drug resistance, the test will correctly classify 766 people as not having second-line injectable drug resistance and misclassify four people as having resistance (moderate quality evidence).

By direct testing, the test detected 94% of people with second-line injectable drug resistance and rarely gave a positive result for people without resistance (very low quality evidence).

XDR-TB
By indirect testing, the test detected 71% of people with XDR-TB and rarely gave a positive result for people without XDR-TB. In a population of 1000 people, where 80 have XDR-TB, MTBDRsl will correctly identify 57 people with XDR-TB and miss 23 people. In this same population of 1000 people, where 920 do not have XDR-TB, the test will correctly classify 909 people as not having XDR-TB and misclassify 11 people as having XDR-TB (low quality evidence).

There was insufficient evidence to determine the accuracy of MTBDRsl by direct testing for XDR-TB.

Conclusions
The results show that a positive MTBDRsl result for resistance to the fluoroquinolone drugs or the second-line injectable drugs is reliable evidence that the person has drug-resistant TB and further conventional drug-resistance testing is not required. However, when the test reports a negative result, clinicians may still wish to carry out conventional testing.