This molecular assay is a highly accurate screening tool for MDR TB, which achieves a substantial reduction in diagnostic delay. With overall performance characteristics that are superior to conventional culture and drug susceptibility testing and the possibility for high throughput with substantial cost savings, molecular testing has the potential to revolutionize MDR TB diagnosis.

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c Molecular diagnostics for Mycobacterium tuberculosis have recently been endorsed by the World Health Organization. The Xpert MTB/RIF assay was endorsed for use on patient material, regardless of smear gradation, while the GenoType MTBDRplus (version 1) has been limited for use on smear-positive patient material. In this study, we evaluated the diagnostic performance of the Xpert MTB/RIF and GenoType MTBDRplus (version 2) assays on smear-positive and smear-negative patient specimens submitted to a high-throughput diagnostic laboratory. A total of 282 consecutive specimens were subjected to the two new molecular assays, and their performance characteristics were assessed relative to the routine diagnostic standard. Both assays showed similar diagnostic performance characteristics. The sensitivities of the GenoType MTBDRplus (v2.0) and Xpert MTB/RIF assays for the detection of culture-positive M. tuberculosis were 73.1% and 71.2%, respectively, while the specificities of both assays were 100%. Both assays were able to diagnose the presence of M. tuberculosis in 57 to 58% of smear-negative cases, suggesting that the performance characteristics were dependent on bacillary load. The detection of M. tuberculosis in culture-negative specimens confirmed that molecular assays should not be used for treatment monitoring. The sensitivity and specificity for rifampin resistance detection were 100% in both assays; however, the GenoType MTBDRplus (v2.0) assay provided additional information on isoniazid susceptibility. The GenoType MTBDRplus (v2.0) assay will complement the Xpert MTB/RIF screening assay by validating rifampin susceptibility and providing information on isoniazid susceptibility. In addition, the GenoType MTBDRplus (v2.0) assay will provide pharmacogenetic information that may be critical in guiding appropriate treatment. S mear microscopy is the primary method for screening for tuberculosis (TB) in high-burden countries (29), but its performance characteristics are poor, with a case detection rate of only 56 to 68% (28). This is further reduced to 43 to 51% in patients coinfected with the human immunodeficiency virus (HIV) (7), which often leads to paucibacillary disease (23). In 2010, it was reported that 2 million of the 5.8 million (34.4%) globally notified cases of TB were smear negative (30). In order to improve the sensitivity and specificity of TB diagnostic modalities, it is critical that new, rapid, and reliable diagnostics are developed (29). Culture-based methods have been greatly improved over the past decade and remain the "gold standard" for TB diagnosis. However, the time to positivity is dependent on the replication rate of Mycobacterium tuberculosis complex as well as the bacillary load in the specimen, which may be low in sputum samples from patients with HIV coinfection (9). This implies that the time to a bacteriological culture-based diagnosis may range from weeks to months (20,22). Furthermore, an additional test is required to confirm the presence of M. tuberculosis complex. To address ...

Use of MTBDRplus significantly reduced time to MDR tuberculosis treatment initiation. However, DST reporting to clinics was delayed by more than 1 week due, in part, to laboratory operational delays, including dependence on smear and culture positivity prior to MTBDRplus performance. In addition, once MDR tuberculosis was reported, delays in contacting patients and initiating therapy require improvements in clinical infrastructure.