Bacterial loads measured by the xpert MTB/ RIF assay as markers of culture conversion and bacteriological cure in pulmonary TB

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

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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.

Original languageEnglish (US)
Article numbere0160062
JournalPloS one
Volume11
Issue number8
DOIs
StatePublished - Aug 2016

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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Shenai, S., Ronacher, K., Malherbe, S., Stanley, K., Kriel, M., Winter, J., Peppard, T., Barry, C. E., Wang, J., Dodd, L. E., Via, L. E., Barry, C. E., Walzl, G., & Alland, D. (2016). Bacterial loads measured by the xpert MTB/ RIF assay as markers of culture conversion and bacteriological cure in pulmonary TB. PloS one, 11(8), [e0160062]. https://doi.org/10.1371/journal.pone.0160062