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

• Published in: Journal of clinical microbiology 2016-12, Vol.54 (12), p.3028-3033
• Main Authors: Jayakumar, A, Savic, R M, Everett, C K, Benator, D, Alland, D, Heilig, C M, Weiner, M, Friedrich, S O, Martinson, N A, Kerrigan, A, Zamudio, C, Goldberg, S V, Whitworth, W C, Davis, J L, Nahid, P
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; DNA, Bacterial - genetics; Female; Humans; Male; Middle Aged; Mycobacteriology and Aerobic Actinomycetes; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Rifampin - adverse effects; Rifampin - analogs & derivatives; Rifampin - therapeutic use; Sensitivity and Specificity; Sputum - microbiology; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - drug therapy; Young Adult
• ISSN: 0095-1137; 1098-660X
• DOI: 10.1128/JCM.01313-16

The Xpert MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle threshold (C ) values, which may provide a dynamic measure of sputum bacillary burden when used longitudinally. We evaluated the relationship between Xpert C trajectory and drug exposure during tuberculosis (TB) treatment to assess the potential utility of Xpert C 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 C 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 C 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 C (P = 0.02). The estimated increase in C slope for every additional 100 μg · h/ml of rifapentine drug exposure (as measured by AUC) was 0.11 C /week (95% confidence interval [CI], 0.05 to 0.17). Increasing rifapentine exposure is associated with a higher rate of change of Xpert C , 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.