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PLoS One. 2016 Aug 10;11(8):e0160062. doi: 10.1371/journal.pone.0160062. eCollection 2016.

Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB.

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Division of Infectious Diseases, Rutgers New Jersey Medical School, ^Rutgers Biomedical & Health Sciences (Formerly UMDNJ), 185 South Orange Avenue, Newark, New Jersey, United States of America.
DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology & Human Genetics, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town, South Africa.
Catalysis Foundation for Health, Emeryville, California, United States of America.
Certara, LP, on contract to the Bill and Melinda Gates Foundation, Greater Detroit Area, United States of America.
Brown University, Providence Rhode Islands, United States of America.
Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, Maryland, United States of America.
Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland, United States of America.
Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, United States of America.
Institute of Infectious Disease and Molecular Medicine, and the Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch 7701, South Africa.



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.


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.


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.


Genome loads measured by Xpert provide a potentially-useful biomarker for classifying same day culture status and predicting response to therapy.

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