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

Munsamy, V.; Leisegang, F.; Nabeta, P.; Ruesch-Gerdes, S.; Blakemore, R.; Vadwai, V.; Tahirli, R.; Persing, D.H.; Boehme, C.C.; Zamudio Fuertes, Carlos Eduardo; Alland, D.; Davidow, A.L.; Perkins, M.D.; Nicol, M.; Jones, M.; Rodrigues, C.; Hillemann, D.

dc.contributor.author	Blakemore, R.
dc.contributor.author	Nabeta, P.
dc.contributor.author	Davidow, A.L.
dc.contributor.author	Vadwai, V.
dc.contributor.author	Tahirli, R.
dc.contributor.author	Munsamy, V.
dc.contributor.author	Nicol, M.
dc.contributor.author	Jones, M.
dc.contributor.author	Persing, D.H.
dc.contributor.author	Hillemann, D.
dc.contributor.author	Ruesch-Gerdes, S.
dc.contributor.author	Leisegang, F.
dc.contributor.author	Zamudio Fuertes, Carlos Eduardo
dc.contributor.author	Rodrigues, C.
dc.contributor.author	Boehme, C.C.
dc.contributor.author	Perkins, M.D.
dc.contributor.author	Alland, D.
dc.date.accessioned	2022-01-18T19:34:34Z
dc.date.available	2022-01-18T19:34:34Z
dc.date.issued	2011
dc.identifier.uri	https://hdl.handle.net/20.500.12866/11020
dc.description.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.	en_US
dc.language.iso	eng
dc.publisher	American Thoracic Society
dc.relation.ispartofseries	American Journal of Respiratory and Critical Care Medicine
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	Humans	en_US
dc.subject	controlled study	en_US
dc.subject	major clinical study	en_US
dc.subject	diagnostic test	en_US
dc.subject	disease severity	en_US
dc.subject	quantitative analysis	en_US
dc.subject	Algorithms	en_US
dc.subject	bacterial load	en_US
dc.subject	Bacterial Proteins	en_US
dc.subject	Clinical trial	en_US
dc.subject	Diagnosis	en_US
dc.subject	Diagnostic techniques and procedures	en_US
dc.subject	DNA, Bacterial	en_US
dc.subject	infection control	en_US
dc.subject	Microscopy	en_US
dc.subject	Molecular diagnostics	en_US
dc.subject	Multicenter Studies as Topic	en_US
dc.subject	Mycobacterium tuberculosis	en_US
dc.subject	Nucleic Acid Amplification Techniques	en_US
dc.subject	Predictive Value of Tests	en_US
dc.subject	Randomized Controlled Trials as Topic	en_US
dc.subject	Real-Time Polymerase Chain Reaction	en_US
dc.subject	Research Design	en_US
dc.subject	Sensitivity and Specificity	en_US
dc.subject	Sputum	en_US
dc.subject	Tuberculosis	en_US
dc.title	A multisite assessment of the quantitative capabilities of the Xpert MTB/RIF assay	en_US
dc.type	info:eu-repo/semantics/article
dc.identifier.doi	https://doi.org/10.1164/rccm.201103-0536OC
dc.subject.ocde	https://purl.org/pe-repo/ocde/ford#3.02.07
dc.relation.issn	1535-4970