Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB.
<h4>Introduction</h4>Biomarkers are needed to monitor tuberculosis (TB) treatment and predict treatment outcomes. We evaluated the Xpert MTB/RIF (Xpert) assay as a biomarker for TB treatment during and at the end of the 24 weeks therapy.<h4>Methods</h4>Sputum from 108 HIV-neg...
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0160062&type=printable |
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| author | Shubhada Shenai Katharina Ronacher Stefanus Malherbe Kim Stanley Magdalena Kriel Jill Winter Thomas Peppard Charles E Barry Jing Wang Lori E Dodd Laura E Via Clifton E Barry Gerhard Walzl David Alland |
| author_facet | Shubhada Shenai Katharina Ronacher Stefanus Malherbe Kim Stanley Magdalena Kriel Jill Winter Thomas Peppard Charles E Barry Jing Wang Lori E Dodd Laura E Via Clifton E Barry Gerhard Walzl David Alland |
| author_sort | Shubhada Shenai |
| collection | DOAJ |
| description | <h4>Introduction</h4>Biomarkers are needed to monitor tuberculosis (TB) treatment and predict treatment outcomes. We evaluated the Xpert MTB/RIF (Xpert) assay as a biomarker for TB treatment during and at the end of the 24 weeks therapy.<h4>Methods</h4>Sputum from 108 HIV-negative, culture-positive pulmonary TB patients was analyzed using Xpert at time points before and during anti-TB therapy. Results were compared against culture. Direct Xpert cycle-threshold (Ct), a change in the Ct (delta Ct), or a novel "percent closing of baseline Ct deficit" (percent closing) were evaluated as classifiers of same-day and end-of-treatment culture and therapeutic outcomes.<h4>Results</h4>Xpert was positive in 29/95 (30.5%) of subjects at week 24; and positive one year after treatment in 8/64 (12.5%) successfully-treated patients who remained free of tuberculosis. We identified a relationship between initial bacterial load measured by baseline Xpert Ct and time to culture conversion (hazard ratio 1.06, p = 0.0023), and to the likelihood of being among the 8 treatment failures at week 24 (AUC = 72.8%). Xpert Ct was even more strongly associated with culture conversion on the day the test was performed with AUCs 96.7%, 99.2%, 86.0% and 90.2%, at Day 7, Week 4, 8 and 24, respectively. Compared to baseline Ct measures alone, a combined measure of baseline Ct plus either Delta Ct or percent closing improved the classification of treatment failure status to a 75% sensitivity and 88.9% specificity.<h4>Conclusions</h4>Genome loads measured by Xpert provide a potentially-useful biomarker for classifying same day culture status and predicting response to therapy. |
| format | Article |
| id | doaj-art-3b4244efac984fadae2e704b9d4bf604 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-3b4244efac984fadae2e704b9d4bf6042025-08-20T02:03:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01118e016006210.1371/journal.pone.0160062Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB.Shubhada ShenaiKatharina RonacherStefanus MalherbeKim StanleyMagdalena KrielJill WinterThomas PeppardCharles E BarryJing WangLori E DoddLaura E ViaClifton E BarryGerhard WalzlDavid Alland<h4>Introduction</h4>Biomarkers are needed to monitor tuberculosis (TB) treatment and predict treatment outcomes. We evaluated the Xpert MTB/RIF (Xpert) assay as a biomarker for TB treatment during and at the end of the 24 weeks therapy.<h4>Methods</h4>Sputum from 108 HIV-negative, culture-positive pulmonary TB patients was analyzed using Xpert at time points before and during anti-TB therapy. Results were compared against culture. Direct Xpert cycle-threshold (Ct), a change in the Ct (delta Ct), or a novel "percent closing of baseline Ct deficit" (percent closing) were evaluated as classifiers of same-day and end-of-treatment culture and therapeutic outcomes.<h4>Results</h4>Xpert was positive in 29/95 (30.5%) of subjects at week 24; and positive one year after treatment in 8/64 (12.5%) successfully-treated patients who remained free of tuberculosis. We identified a relationship between initial bacterial load measured by baseline Xpert Ct and time to culture conversion (hazard ratio 1.06, p = 0.0023), and to the likelihood of being among the 8 treatment failures at week 24 (AUC = 72.8%). Xpert Ct was even more strongly associated with culture conversion on the day the test was performed with AUCs 96.7%, 99.2%, 86.0% and 90.2%, at Day 7, Week 4, 8 and 24, respectively. Compared to baseline Ct measures alone, a combined measure of baseline Ct plus either Delta Ct or percent closing improved the classification of treatment failure status to a 75% sensitivity and 88.9% specificity.<h4>Conclusions</h4>Genome loads measured by Xpert provide a potentially-useful biomarker for classifying same day culture status and predicting response to therapy.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0160062&type=printable |
| spellingShingle | Shubhada Shenai Katharina Ronacher Stefanus Malherbe Kim Stanley Magdalena Kriel Jill Winter Thomas Peppard Charles E Barry Jing Wang Lori E Dodd Laura E Via Clifton E Barry Gerhard Walzl David Alland Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB. PLoS ONE |
| title | Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB. |
| title_full | Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB. |
| title_fullStr | Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB. |
| title_full_unstemmed | Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB. |
| title_short | Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB. |
| title_sort | bacterial loads measured by the xpert mtb rif assay as markers of culture conversion and bacteriological cure in pulmonary tb |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0160062&type=printable |
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