A multisite assessment of the quantitative capabilities of the Xpert MTB/RIF assay

Robert Blakemore, Pamela Nabeta, Amy L. Davidow, Viral Vadwai, Rasim Tahirli, Vanisha Munsamy, Mark Nicol, Martin Jones, David H. Persing, Doris Hillemann, Sabine Ruesch-Gerdes, Felicity Leisegang, Carlos Zamudio, Camilla Rodrigues, Catharina C. Boehme, Mark D. Perkins, David Alland

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Rationale: The Xpert MTB/RIF is an automated molecular test for Mycobacterium tuberculosis that estimates bacterial burden by measuring the threshold-cycle (Ct) of its M. tuberculosis-specific real-time polymerase chain reaction. Bacterialburden is an important biomarker for disease severity, infection control risk, and response to therapy. Objectives: Evaluate bacterial load quantitation by Xpert MTB/RIF compared with conventional quantitative methods. Methods: Xpert MTB/RIF results we recompared with smear-microscopy, semiquantiative solid culture, and time-to-detection in liquid culture for 741 patients and 2,008 samples tested in a multisite clinical trial. An internal control real-time polymerase chain reaction was evaluated for its ability to identify inaccurate quantitative Xpert MTB/RIF results. Measurements and Main Results: Assays with an internal control Ct greater than 34 were likely to be inaccurately quantitated; this represented 15% of M. tuberculosis-positive tests. Excluding these, decreasing M. tuberculosis Ct was associated with increasing smear microscopy grade for smears of concentrated sputum pellets (r s = 20.77) and directly from sputum (r s = -0.71). A Ct cutoff of approximately 27.7 best predicted smear-positive status. The association between M. tuberculosis Ct and time-to-detection in liquid culture (r s = 0.68) andsemiquantitative colony counts (r s = -0.56)wasweaker than smear. Tests of paired same-patient sputum showed that highviscosity sputum samples contained x32 more M. tuberculosis than nonviscous samples. Comparisons between the grade of the acid-fast bacilli smear and Xpert MTB/RIF quantitative data across study sites enabled us to identify a site outlier inmicroscopy. Conclusions: Xpert MTB/RIF quantitation offers a new, standardized approach to measuring bacterial burden in the sputum of patients with tuberculosis.

Original languageEnglish (US)
Pages (from-to)1076-1084
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Volume184
Issue number9
DOIs
StatePublished - Nov 1 2011

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Keywords

  • Clinical trial
  • Diagnosis
  • Diagnostic techniques and procedures
  • Molecular diagnostics
  • Tuberculosis

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    Blakemore, R., Nabeta, P., Davidow, A. L., Vadwai, V., Tahirli, R., Munsamy, V., Nicol, M., Jones, M., Persing, D. H., Hillemann, D., Ruesch-Gerdes, S., Leisegang, F., Zamudio, C., Rodrigues, C., Boehme, C. C., Perkins, M. D., & Alland, D. (2011). A multisite assessment of the quantitative capabilities of the Xpert MTB/RIF assay. American journal of respiratory and critical care medicine, 184(9), 1076-1084. https://doi.org/10.1164/rccm.201103-0536OC