The New Xpert MTB/RIF Ultra: Improving Detection of <italic toggle="yes">Mycobacterium tuberculosis</italic> and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing
ABSTRACT The Xpert MTB/RIF assay (Xpert) is a rapid test for tuberculosis (TB) and rifampin resistance (RIF-R) suitable for point-of-care testing. However, it has decreased sensitivity in smear-negative sputum, and false identification of RIF-R occasionally occurs. We developed the Xpert MTB/RIF Ult...
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American Society for Microbiology
2017
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oai:doaj.org-article:751391a3a1084ef2b8c600d6d58453e02021-11-15T15:51:44ZThe New Xpert MTB/RIF Ultra: Improving Detection of <italic toggle="yes">Mycobacterium tuberculosis</italic> and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing10.1128/mBio.00812-172150-7511https://doaj.org/article/751391a3a1084ef2b8c600d6d58453e02017-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00812-17https://doaj.org/toc/2150-7511ABSTRACT The Xpert MTB/RIF assay (Xpert) is a rapid test for tuberculosis (TB) and rifampin resistance (RIF-R) suitable for point-of-care testing. However, it has decreased sensitivity in smear-negative sputum, and false identification of RIF-R occasionally occurs. We developed the Xpert MTB/RIF Ultra assay (Ultra) to improve performance. Ultra and Xpert limits of detection (LOD), dynamic ranges, and RIF-R rpoB mutation detection were tested on Mycobacterium tuberculosis DNA or sputum samples spiked with known numbers of M. tuberculosis H37Rv or Mycobacterium bovis BCG CFU. Frozen and prospectively collected clinical samples from patients suspected of having TB, with and without culture-confirmed TB, were also tested. For M. tuberculosis H37Rv, the LOD was 15.6 CFU/ml of sputum for Ultra versus 112.6 CFU/ml of sputum for Xpert, and for M. bovis BCG, it was 143.4 CFU/ml of sputum for Ultra versus 344 CFU/ml of sputum for Xpert. Ultra resulted in no false-positive RIF-R specimens, while Xpert resulted in two false-positive RIF-R specimens. All RIF-R-associated M. tuberculosis rpoB mutations tested were identified by Ultra. Testing on clinical sputum samples, Ultra versus Xpert, resulted in an overall sensitivity of 87.5% (95% confidence interval [CI], 82.1, 91.7) versus 81.0% (95% CI, 74.9, 86.2) and a sensitivity on sputum smear-negative samples of 78.9% (95% CI, 70.0, 86.1) versus 66.1% (95% CI, 56.4, 74.9). Both tests had a specificity of 98.7% (95% CI, 93.0, 100), and both had comparable accuracies for detection of RIF-R in these samples. Ultra should significantly improve TB detection, especially in patients with paucibacillary disease, and may provide more-reliable RIF-R detection. IMPORTANCE The Xpert MTB/RIF assay (Xpert), the first point-of-care assay for tuberculosis (TB), was endorsed by the World Health Organization in December 2010. Since then, 23 million Xpert tests have been procured in 130 countries. Although Xpert showed high overall sensitivity and specificity with pulmonary samples, its sensitivity has been lower with smear-negative pulmonary samples and extrapulmonary samples. In addition, the prediction of rifampin resistance (RIF-R) in paucibacillary samples and for a few rpoB mutations has resulted in both false-positive and false-negative results. The present study is the first demonstration of the design features and operational characteristics of an improved Xpert Ultra assay. This study also shows that the Ultra format overcomes many of the known shortcomings of Xpert. The new assay should significantly improve TB detection, especially in patients with paucibacillary disease, and provide more-reliable detection of RIF-R.Soumitesh ChakravortyAnn Marie SimmonsMazhgan RownekiHeta ParmarYuan CaoJamie RyanPadmapriya P. BanadaSrinidhi DeshpandeShubhada ShenaiAlexander GallJennifer GlassBarry KrieswirthSamuel G. SchumacherPamela NabetaNestani TukvadzeCamilla RodriguesAlena SkrahinaElisa TaglianiDaniela M. CirilloAmy DavidowClaudia M. DenkingerDavid PersingRobert KwiatkowskiMartin JonesDavid AllandAmerican Society for MicrobiologyarticleXpert MTB/RIF UltradiagnosissensitivetuberculosisMicrobiologyQR1-502ENmBio, Vol 8, Iss 4 (2017) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Xpert MTB/RIF Ultra diagnosis sensitive tuberculosis Microbiology QR1-502 |
| spellingShingle |
Xpert MTB/RIF Ultra diagnosis sensitive tuberculosis Microbiology QR1-502 Soumitesh Chakravorty Ann Marie Simmons Mazhgan Rowneki Heta Parmar Yuan Cao Jamie Ryan Padmapriya P. Banada Srinidhi Deshpande Shubhada Shenai Alexander Gall Jennifer Glass Barry Krieswirth Samuel G. Schumacher Pamela Nabeta Nestani Tukvadze Camilla Rodrigues Alena Skrahina Elisa Tagliani Daniela M. Cirillo Amy Davidow Claudia M. Denkinger David Persing Robert Kwiatkowski Martin Jones David Alland The New Xpert MTB/RIF Ultra: Improving Detection of <italic toggle="yes">Mycobacterium tuberculosis</italic> and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing |
| description |
ABSTRACT The Xpert MTB/RIF assay (Xpert) is a rapid test for tuberculosis (TB) and rifampin resistance (RIF-R) suitable for point-of-care testing. However, it has decreased sensitivity in smear-negative sputum, and false identification of RIF-R occasionally occurs. We developed the Xpert MTB/RIF Ultra assay (Ultra) to improve performance. Ultra and Xpert limits of detection (LOD), dynamic ranges, and RIF-R rpoB mutation detection were tested on Mycobacterium tuberculosis DNA or sputum samples spiked with known numbers of M. tuberculosis H37Rv or Mycobacterium bovis BCG CFU. Frozen and prospectively collected clinical samples from patients suspected of having TB, with and without culture-confirmed TB, were also tested. For M. tuberculosis H37Rv, the LOD was 15.6 CFU/ml of sputum for Ultra versus 112.6 CFU/ml of sputum for Xpert, and for M. bovis BCG, it was 143.4 CFU/ml of sputum for Ultra versus 344 CFU/ml of sputum for Xpert. Ultra resulted in no false-positive RIF-R specimens, while Xpert resulted in two false-positive RIF-R specimens. All RIF-R-associated M. tuberculosis rpoB mutations tested were identified by Ultra. Testing on clinical sputum samples, Ultra versus Xpert, resulted in an overall sensitivity of 87.5% (95% confidence interval [CI], 82.1, 91.7) versus 81.0% (95% CI, 74.9, 86.2) and a sensitivity on sputum smear-negative samples of 78.9% (95% CI, 70.0, 86.1) versus 66.1% (95% CI, 56.4, 74.9). Both tests had a specificity of 98.7% (95% CI, 93.0, 100), and both had comparable accuracies for detection of RIF-R in these samples. Ultra should significantly improve TB detection, especially in patients with paucibacillary disease, and may provide more-reliable RIF-R detection. IMPORTANCE The Xpert MTB/RIF assay (Xpert), the first point-of-care assay for tuberculosis (TB), was endorsed by the World Health Organization in December 2010. Since then, 23 million Xpert tests have been procured in 130 countries. Although Xpert showed high overall sensitivity and specificity with pulmonary samples, its sensitivity has been lower with smear-negative pulmonary samples and extrapulmonary samples. In addition, the prediction of rifampin resistance (RIF-R) in paucibacillary samples and for a few rpoB mutations has resulted in both false-positive and false-negative results. The present study is the first demonstration of the design features and operational characteristics of an improved Xpert Ultra assay. This study also shows that the Ultra format overcomes many of the known shortcomings of Xpert. The new assay should significantly improve TB detection, especially in patients with paucibacillary disease, and provide more-reliable detection of RIF-R. |
| format |
article |
| author |
Soumitesh Chakravorty Ann Marie Simmons Mazhgan Rowneki Heta Parmar Yuan Cao Jamie Ryan Padmapriya P. Banada Srinidhi Deshpande Shubhada Shenai Alexander Gall Jennifer Glass Barry Krieswirth Samuel G. Schumacher Pamela Nabeta Nestani Tukvadze Camilla Rodrigues Alena Skrahina Elisa Tagliani Daniela M. Cirillo Amy Davidow Claudia M. Denkinger David Persing Robert Kwiatkowski Martin Jones David Alland |
| author_facet |
Soumitesh Chakravorty Ann Marie Simmons Mazhgan Rowneki Heta Parmar Yuan Cao Jamie Ryan Padmapriya P. Banada Srinidhi Deshpande Shubhada Shenai Alexander Gall Jennifer Glass Barry Krieswirth Samuel G. Schumacher Pamela Nabeta Nestani Tukvadze Camilla Rodrigues Alena Skrahina Elisa Tagliani Daniela M. Cirillo Amy Davidow Claudia M. Denkinger David Persing Robert Kwiatkowski Martin Jones David Alland |
| author_sort |
Soumitesh Chakravorty |
| title |
The New Xpert MTB/RIF Ultra: Improving Detection of <italic toggle="yes">Mycobacterium tuberculosis</italic> and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing |
| title_short |
The New Xpert MTB/RIF Ultra: Improving Detection of <italic toggle="yes">Mycobacterium tuberculosis</italic> and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing |
| title_full |
The New Xpert MTB/RIF Ultra: Improving Detection of <italic toggle="yes">Mycobacterium tuberculosis</italic> and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing |
| title_fullStr |
The New Xpert MTB/RIF Ultra: Improving Detection of <italic toggle="yes">Mycobacterium tuberculosis</italic> and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing |
| title_full_unstemmed |
The New Xpert MTB/RIF Ultra: Improving Detection of <italic toggle="yes">Mycobacterium tuberculosis</italic> and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing |
| title_sort |
new xpert mtb/rif ultra: improving detection of <italic toggle="yes">mycobacterium tuberculosis</italic> and resistance to rifampin in an assay suitable for point-of-care testing |
| publisher |
American Society for Microbiology |
| publishDate |
2017 |
| url |
https://doaj.org/article/751391a3a1084ef2b8c600d6d58453e0 |
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