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Xpert MTB/RIF Assay Shows Faster Clearance of Mycobacterium tuberculosis DNA with Higher Levels of Rifapentine Exposure

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dc.contributor.author Jayakumar, A.
dc.contributor.author Savic, R. M.
dc.contributor.author Everett, C. K.
dc.contributor.author Benator, D.
dc.contributor.author Alland, D.
dc.contributor.author Heilig, C. M.
dc.contributor.author Weiner, M.
dc.contributor.author Friedrich, S. O.
dc.contributor.author Martinson, N. A.
dc.contributor.author Kerrigan, A.
dc.contributor.author Zamudio, C.
dc.contributor.author Goldberg, S. V.
dc.contributor.author Whitworth, W. C.
dc.contributor.author Davis, J. L.
dc.contributor.author Nahid, P.
dc.date.accessioned 2019-02-06T14:45:35Z
dc.date.available 2019-02-06T14:45:35Z
dc.date.issued 2016
dc.identifier.uri https://hdl.handle.net/20.500.12866/5092
dc.description.abstract The Xpert MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle threshold (CT) values, 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 tuberculosis (TB) treatment to assess the potential utility of Xpert CT for treatment monitoring. We obtained serial sputum samples from patients with smear-positive pulmonary TB who were consecutively enrolled at 10 international clinical trial sites participating in study 29X, a CDC-sponsored Tuberculosis Trials Consortium study evaluating the tolerability, safety, and antimicrobial activity of rifapentine at daily doses of up to 20 mg/kg of body weight. 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 than 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 mug . h/ml of rifapentine drug exposure (as measured by AUC) was 0.11 CT/week (95% confidence interval [CI], 0.05 to 0.17). Increasing rifapentine exposure is associated with a higher rate of change of Xpert CT, indicating faster clearance of Mycobacterium tuberculosis 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. en_US
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.relation.ispartof urn:issn:1098-660X
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Adolescent en_US
dc.subject Adult en_US
dc.subject DNA, Bacterial/genetics en_US
dc.subject Female en_US
dc.subject Humans en_US
dc.subject Male en_US
dc.subject Middle Aged en_US
dc.subject Mycobacterium tuberculosis/drug effects/genetics en_US
dc.subject Rifampin/adverse effects/analogs & derivatives/therapeutic use en_US
dc.subject Sensitivity and Specificity en_US
dc.subject Sputum/microbiology en_US
dc.subject Tuberculosis, Pulmonary/diagnosis/drug therapy en_US
dc.subject Young Adult en_US
dc.title Xpert MTB/RIF Assay Shows Faster Clearance of Mycobacterium tuberculosis DNA with Higher Levels of Rifapentine Exposure en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1128/JCM.01313-16
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.01

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