title: Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB.
abstract: BACKGROUND
  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.
authors: 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.
authors: Shubhada
authors: S
authors: Shenai
authors: 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.
authors: Katharina
authors: K
authors: Ronacher
authors: 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.
authors: Stefanus
authors: S
authors: Malherbe
authors: 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.
authors: Kim
authors: K
authors: Stanley
authors: 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.
authors: Magdalena
authors: M
authors: Kriel
authors: Catalysis Foundation for Health, Emeryville, California, United States of America.
authors: Jill
authors: J
authors: Winter
authors: Certara, LP, on contract to the Bill and Melinda Gates Foundation, Greater Detroit Area, United States of America.
authors: Thomas
authors: T
authors: Peppard
authors: Brown University, Providence Rhode Islands, United States of America.
authors: Charles E
authors: CE
authors: Barry
authors: Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, Maryland, United States of America.
authors: Jing
authors: J
authors: Wang
authors: Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland, United States of America.
authors: Lori E
authors: LE
authors: Dodd
authors: 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.
authors: Laura E
authors: LE
authors: Via
authors: 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.
authors: Clifton E
authors: CE
authors: Barry
authors: 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.
authors: Gerhard
authors: G
authors: Walzl
authors: 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.
authors: David
authors: D
authors: Alland
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D019540:Area Under Curve; D058491:Bacterial Load; D001431:Bacteriological Techniques / Q000592:standards*; D015415:Biomarkers / Q000032:analysis*; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011718:Pyrazinamide / Q000627:therapeutic use; D012372:ROC Curve; D012680:Sensitivity and Specificity; D017211:Treatment Failure; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid