title: Xpert MTB/RIF Assay Shows Faster Clearance of Mycobacterium tuberculosis DNA with Higher Levels of Rifapentine Exposure.
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 CTtrajectory and drug exposure during tuberculosis (TB) treatment to assess the potential utility of Xpert CTfor 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 CTdata 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 CTwas 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 CTslope for every additional 100 μg · 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.
authors.affiliation: University of California, San Francisco, Division of Pulmonary and Critical Care Medicine, San Francisco, California, USA.
authors.forename: A
authors.initials: A
authors.lastname: Jayakumar
authors.affiliation: University of California, San Francisco, School of Pharmacy, San Francisco, California, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Savic
authors.affiliation: University of California, San Francisco, Division of Pulmonary and Critical Care Medicine, San Francisco, California, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Everett
authors.affiliation: Washington DC VA Medical Center and the George Washington University, Washington, DC, USA.
authors.forename: D
authors.initials: D
authors.lastname: Benator
authors.affiliation: Rutgers-New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: D
authors.initials: D
authors.lastname: Alland
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Heilig
authors.affiliation: Veterans Administration Medical Center and University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: M
authors.initials: M
authors.lastname: Weiner
authors.affiliation: Division of Medical Physiology, MRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors.forename: S O
authors.initials: SO
authors.lastname: Friedrich
authors.affiliation: Perinatal HIV Research Unit (PHRU), MRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: N A
authors.initials: NA
authors.lastname: Martinson
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kerrigan
authors.affiliation: Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: C
authors.initials: C
authors.lastname: Zamudio
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Goldberg
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Whitworth
authors.affiliation: Yale School of Public Health, New Haven, Connecticut, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Davis
authors.affiliation: University of California, San Francisco, Division of Pulmonary and Critical Care Medicine, San Francisco, California, USA pnahid@ucsf.edu.
authors.forename: P
authors.initials: P
authors.lastname: Nahid
mesh_terms: D000293:Adolescent; D000328:Adult; D004269:DNA, Bacterial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D012293:Rifampin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial; D012293:Rifampin; C018421:rifapentine