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. Bacterial burden 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 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 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) = -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. CONCLUSIONS: Xpert MTB/RIF quantitation offers a new, standardized approach to measuring bacterial burden in the sputum of patients with tuberculosis.
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. Bacterial burden 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 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 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) = -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. CONCLUSIONS: Xpert MTB/RIF quantitation offers a new, standardized approach to measuring bacterial burden in the sputum of patients with tuberculosis.
Authors: M Ruddy; T D McHugh; J W Dale; D Banerjee; H Maguire; P Wilson; F Drobniewski; P Butcher; S H Gillespie Journal: J Clin Microbiol Date: 2002-11 Impact factor: 5.948
Authors: Grant Theron; Jonny Peter; Richard van Zyl-Smit; Hridesh Mishra; Elizabeth Streicher; Samuel Murray; Rodney Dawson; Andrew Whitelaw; Michael Hoelscher; Surendra Sharma; Madhukar Pai; Robin Warren; Keertan Dheda Journal: Am J Respir Crit Care Med Date: 2011-04-14 Impact factor: 21.405
Authors: Susan E Dorman; Payam Nahid; Ekaterina V Kurbatova; Stefan V Goldberg; Lorna Bozeman; William J Burman; Kwok-Chiu Chang; Michael Chen; Mark Cotton; Kelly E Dooley; Melissa Engle; Pei-Jean Feng; Courtney V Fletcher; Phan Ha; Charles M Heilig; John L Johnson; Erica Lessem; Beverly Metchock; Jose M Miro; Nguyen Viet Nhung; April C Pettit; Patrick P J Phillips; Anthony T Podany; Anne E Purfield; Kathleen Robergeau; Wadzanai Samaneka; Nigel A Scott; Erin Sizemore; Andrew Vernon; Marc Weiner; Susan Swindells; Richard E Chaisson Journal: Contemp Clin Trials Date: 2020-01-22 Impact factor: 2.226
Authors: Karen R Steingart; Ian Schiller; David J Horne; Madhukar Pai; Catharina C Boehme; Nandini Dendukuri Journal: Cochrane Database Syst Rev Date: 2014-01-21
Authors: Colleen F Hanrahan; Grant Theron; Jean Bassett; Keertan Dheda; Lesley Scott; Wendy Stevens; Ian Sanne; Annelies Van Rie Journal: Am J Respir Crit Care Med Date: 2014-06-01 Impact factor: 21.405
Authors: Karen R Steingart; Hojoon Sohn; Ian Schiller; Lorie A Kloda; Catharina C Boehme; Madhukar Pai; Nandini Dendukuri Journal: Cochrane Database Syst Rev Date: 2013-01-31
Authors: Xavier A Kayigire; Sven O Friedrich; Amour Venter; Rodney Dawson; Stephen H Gillespie; Martin J Boeree; Norbert Heinrich; Michael Hoelscher; Andreas H Diacon Journal: J Clin Microbiol Date: 2013-04-17 Impact factor: 5.948