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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.

Author information

1
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.
2
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.
3
Catalysis Foundation for Health, Emeryville, California, United States of America.
4
Certara, LP, on contract to the Bill and Melinda Gates Foundation, Greater Detroit Area, United States of America.
5
Brown University, Providence Rhode Islands, United States of America.
6
Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, Maryland, United States of America.
7
Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland, United States of America.
8
Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, United States of America.
9
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.

Abstract

INTRODUCTION:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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

PMID:
27508390
PMCID:
PMC4980126
DOI:
10.1371/journal.pone.0160062
[Indexed for MEDLINE]
Free PMC Article

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