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Wednesday, 07 September 2016 08:27

Paper 2016_08

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A) Comment on: Delamanid susceptibility testing of Mycobacterium tuberculosis using the resazurin microtitre assay and the BACTEC™ MGIT™ 960 system   Comment by Graham Bothamley: Drug sensitivity testing for delaminid meets unexpected problems.  The manufacturers of delaminid, and coincidentally sponsors of the European Respiratory Society’s TB consilium, are called to account regarding drug sensitivity testing for delaminid.     B) Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB.

Shenai S1, Ronacher K2, Malherbe S2, Stanley K2, Kriel M2, Winter J3, Peppard T4, Barry CE5, Wang J6, Dodd LE7, Via LE8,9, Barry CE 3rd8,9, Walzl G2, Alland D1.



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.


Comment by Graham Bothamley: Cycle threshold in Xpert MTB/RIF at the level of detection (25 to 40 Ct) are suggested to monitor treatment.  At the end of successful treatment, 31% remain positive (Ct >40), and 12.5% remain positive a year after successful treatment has been completed. 





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