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

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

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.

MeSH terms

  • Antitubercular Agents / therapeutic use
  • Area Under Curve
  • Bacterial Load
  • Bacteriological Techniques / standards*
  • Biomarkers / analysis*
  • Ethambutol / therapeutic use
  • Female
  • Humans
  • Isoniazid / therapeutic use
  • Male
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / isolation & purification
  • Mycobacterium tuberculosis / metabolism
  • Pyrazinamide / therapeutic use
  • ROC Curve
  • Sensitivity and Specificity
  • Treatment Failure
  • Tuberculosis, Pulmonary / diagnosis*
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / microbiology*

Substances

  • Antitubercular Agents
  • Biomarkers
  • Pyrazinamide
  • Ethambutol
  • Isoniazid