title: Rapid molecular detection of tuberculosis and rifampin resistance.
abstract: BACKGROUND
  Global control of tuberculosis is hampered by slow, insensitive diagnostic methods, particularly for the detection of drug-resistant forms and in patients with human immunodeficiency virus infection. Early detection is essential to reduce the death rate and interrupt transmission, but the complexity and infrastructure needs of sensitive methods limit their accessibility and effect.
  
  
  METHODS
  We assessed the performance of Xpert MTB/RIF, an automated molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF), with fully integrated sample processing in 1730 patients with suspected drug-sensitive or multidrug-resistant pulmonary tuberculosis. Eligible patients in Peru, Azerbaijan, South Africa, and India provided three sputum specimens each. Two specimens were processed with N-acetyl-L-cysteine and sodium hydroxide before microscopy, solid and liquid culture, and the MTB/RIF test, and one specimen was used for direct testing with microscopy and the MTB/RIF test.
  
  
  RESULTS
  Among culture-positive patients, a single, direct MTB/RIF test identified 551 of 561 patients with smear-positive tuberculosis (98.2%) and 124 of 171 with smear-negative tuberculosis (72.5%). The test was specific in 604 of 609 patients without tuberculosis (99.2%). Among patients with smear-negative, culture-positive tuberculosis, the addition of a second MTB/RIF test increased sensitivity by 12.6 percentage points and a third by 5.1 percentage points, to a total of 90.2%. As compared with phenotypic drug-susceptibility testing, MTB/RIF testing correctly identified 200 of 205 patients (97.6%) with rifampin-resistant bacteria and 504 of 514 (98.1%) with rifampin-sensitive bacteria. Sequencing resolved all but two cases in favor of the MTB/RIF assay.
  
  
  CONCLUSIONS
  The MTB/RIF test provided sensitive detection of tuberculosis and rifampin resistance directly from untreated sputum in less than 2 hours with minimal hands-on time. (Funded by the Foundation for Innovative New Diagnostics.)
authors.affiliation: Foundation for Innovative New Diagnostics, Geneva, Switzerland. catharina.boehme@finddiagnostics.org
authors.forename: Catharina C
authors.initials: CC
authors.lastname: Boehme
authors.forename: Pamela
authors.initials: P
authors.lastname: Nabeta
authors.forename: Doris
authors.initials: D
authors.lastname: Hillemann
authors.forename: Mark P
authors.initials: MP
authors.lastname: Nicol
authors.forename: Shubhada
authors.initials: S
authors.lastname: Shenai
authors.forename: Fiorella
authors.initials: F
authors.lastname: Krapp
authors.forename: Jenny
authors.initials: J
authors.lastname: Allen
authors.forename: Rasim
authors.initials: R
authors.lastname: Tahirli
authors.forename: Robert
authors.initials: R
authors.lastname: Blakemore
authors.forename: Roxana
authors.initials: R
authors.lastname: Rustomjee
authors.forename: Ana
authors.initials: A
authors.lastname: Milovic
authors.forename: Martin
authors.initials: M
authors.lastname: Jones
authors.forename: Sean M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: David H
authors.initials: DH
authors.lastname: Persing
authors.forename: Sabine
authors.initials: S
authors.lastname: Ruesch-Gerdes
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gotuzzo
authors.forename: Camilla
authors.initials: C
authors.lastname: Rodrigues
authors.forename: David
authors.initials: D
authors.lastname: Alland
authors.forename: Mark D
authors.initials: MD
authors.lastname: Perkins
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D012321:DNA-Directed RNA Polymerases; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000295:instrumentation / Q000379:methods*; D011446:Prospective Studies; D012015:Reference Standards; D012293:Rifampin / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D014376:Tuberculosis / Q000175:diagnosis / Q000382:microbiology*; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin
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