domingo, 30 de octubre de 2016

Xpert MTB/RIF Assay shows faster clearance of M. tuberculosis DNA with higher rifapentine exposure. - PubMed - NCBI

Xpert MTB/RIF Assay shows faster clearance of M. tuberculosis DNA with higher rifapentine exposure. - PubMed - NCBI



 2016 Oct 12. pii: JCM.01313-16. [Epub ahead of print]

Xpert MTB/RIF Assay shows faster clearance of M. tuberculosis DNA with higher rifapentine exposure.

Abstract

The Xpert® MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle thresholds (Ct), which may provide a dynamic measure of sputum bacillary burden when used longitudinally. We evaluated the relationship between Xpert Ct trajectory and drug exposure during TB treatment to evaluate the potential utility of Xpert Ct for treatment monitoring. We obtained serial sputum samples from patients with smear-positive pulmonary TB consecutively enrolled at ten international clinical trial sites participating in Study 29X, a CDC-sponsored TB Trials Consortium study evaluating the tolerability, safety, and antimicrobial activity of rifapentine at daily doses up to 20 mg/kg. Xpert was performed at weeks 0, 2, 4, 6, 8, and 12. Longitudinal Ct data were modeled using a nonlinear mixed effects model, in relation to rifapentine exposure (area under the concentration-time curve [AUC]). The rate of change of Ct was higher in subjects receiving rifapentine compared to that in subjects receiving standard dose rifampin. Moreover, rifapentine exposure, but not assigned dose, was significantly associated with rate of change in Ct (p = 0.02). The estimated increase in Ct slope for every additional 100 mcg*h/mL of rifapentine drug exposure (as measured by AUC) was 0.11 Ct/week (95% CI 0.05 - 0.17). Increasing rifapentine exposure is associated with faster rate of change of Xpert Ct, indicating faster clearance of MTB DNA. These data suggest that the quantitative outputs of the Xpert MTB/RIF assay may be useful as a dynamic measure of TB treatment response.

PMID:
 
27733634
 
DOI:
 
10.1128/JCM.01313-16

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