Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings

Authors

Anne F. Luetkemeyer, San Francisco General HospitalFollow
Cynthia Fimhaber, University of the Witwatersrand, Johannesburg
Michelle A. Kendall, Harvard T.H. Chan School
Xingye Wu, Harvard T.H. Chan School
Gerald H. Mazurek, CDC
Debra A. Benator, The George Washington University
Roberto Arduino, The University of Texas Health Science Center at Houston
Michel Femandez, University of North Texas Health Science Center
Elizabeth Guy, Baylor College of Medicine
Pamela Johnson, Keck School of Medicine of USC
Beverly Metchock, CDC
Fred Sattler, Keck School of Medicine of USC
Edward Telzak, Albert Einstein College of Medicine
Yun F. Wang, Emory University School of Medicine
Marc Weiner, University of Texas Health Science Center at San Antonio
Susan Swindells, University of Nebraska Medical CenterFollow
Ian M. Sanne, University of the Witwatersrand, Johannesburg
Diane V. Havlir, San Francisco General Hospital
Beatriz Grinsztejn, Instituto de Pesquisa Clinica Evandro Chagas Fiocruz
David Alland, Rutgers New Jersey Medical School

Date of this Version

2016

Document Type

Article

Citation

Clinical Infectious Diseases® 2016;62(9):1081–8

Comments

© The Author 2016.

This document is a U.S. government work and is not subject to copyright in the United States.

DOI: 10.1093/cid/ciw035

Abstract

Background. The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well as rpoB mutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation.

Methods. Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa.

Results. Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB⁺] sputum, 59.3% with AFB smear-negative [AFB^–] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB⁺, 71.4% if AFB^–), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB⁺/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%.

Conclusions. In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation.