• 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, and David Alland.
• Division of Infectious Disease, Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark, USA.
• Am. J. Respir. Crit. Care Med. 2011 Nov 1; 184 (9): 107610841076-84.

RationaleThe 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. Bacterial burden is an important biomarker for disease severity, infection control risk, and response to therapy.ObjectivesEvaluate bacterial load quantitation by Xpert MTB/RIF compared with conventional quantitative methods.MethodsXpert MTB/RIF results were compared 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 ResultsAssays 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) = -0.77) 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) and semiquantitative colony counts (r(s) = -0.56) was weaker than smear. Tests of paired same-patient sputum showed that high viscosity sputum samples contained ×32 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 in microscopy.ConclusionsXpert MTB/RIF quantitation offers a new, standardized approach to measuring bacterial burden in the sputum of patients with tuberculosis.

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