title: 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.
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 asrpoBmutations 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.
authors.affiliation: Division of HIV, Infectious Diseases and Global Medicine, San Francisco General Hospital, University of California.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Luetkemeyer
authors.affiliation: Clinical HIV Research Unit Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand Right to Care, Johannesburg, South Africa.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Firnhaber
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Kendall
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Xingye
authors.initials: X
authors.lastname: Wu
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Mazurek
authors.affiliation: Infectious Diseases Section, Veterans Affairs Medical Center and The George Washington University, Washington D.C.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Benator
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at Houston.
authors.forename: Roberto
authors.initials: R
authors.lastname: Arduino
authors.affiliation: University of North Texas Health Science Center, Tarrant County Health Department, Fort Worth.
authors.forename: Michel
authors.initials: M
authors.lastname: Fernandez
authors.affiliation: Section of Pulmonary Critical Care and Sleep Medicine, Baylor College of Medicine, Ben Taub General Hospital, Houston, Texas.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Guy
authors.affiliation: Cepheid, Sunnyvale.
authors.forename: Pamela
authors.initials: P
authors.lastname: Johnson
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Beverly
authors.initials: B
authors.lastname: Metchock
authors.affiliation: Division of Infectious Diseases, Keck School of Medicine of USC, Los Angeles, California.
authors.forename: Fred
authors.initials: F
authors.lastname: Sattler
authors.affiliation: St. Barnabus Hospital Health System, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Edward
authors.initials: E
authors.lastname: Telzak
authors.affiliation: Emory University School of Medicine, Grady Memorial Hospital, Atlanta, Georgia.
authors.forename: Yun F
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Department of Medicine, University of Texas Health Science Center, Veterans Administration Medical Center, San Antonio.
authors.forename: Marc
authors.initials: M
authors.lastname: Weiner
authors.affiliation: Internal Medicine/Infectious Diseases, University of Nebraska Medical Center, Lincoln.
authors.forename: Susan
authors.initials: S
authors.lastname: Swindells
authors.affiliation: Right to Care, Johannesburg, South Africa Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Sanne
authors.affiliation: Division of HIV, Infectious Diseases and Global Medicine, San Francisco General Hospital, University of California.
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
authors.affiliation: Infectious Diseases Department, Instituto de Pesquisa Clinica Evandro Chagas Fiocruz, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.affiliation: Division of Infectious Disease, Rutgers New Jersey Medical School, Newark.
authors.forename: David
authors.initials: D
authors.lastname: Alland
mesh_terms: D000328:Adult; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use; D001938:Brazil; D004269:DNA, Bacterial; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics; D021141:Nucleic Acid Amplification Techniques; D015995:Prevalence; D012293:Rifampin / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology; D014481:United States
chemical_list: D000904:Antibiotics, Antitubercular; D004269:DNA, Bacterial; D012293:Rifampin
keywords: HIV/tuberculosis coinfection; Xpert MTB/RIF; nontuberculous mycobacteria; respiratory isolation; tuberculosis diagnosis
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