title: Shortening Isolation of Patients With Suspected Tuberculosis by Using Polymerase Chain Reaction Analysis: A Nationwide Cross-sectional Study.
abstract: BACKGROUND
  Isolation of patients suspected for pulmonary tuberculosis is guided by serial sputum smears. This can result in isolation for days for patients with noncontagious tuberculosis. To determine whether a single sample negative for Mycobacterium tuberculosis complex at polymerase chain reaction (PCR) can guide isolation.
  
  
  METHODS
  We retrospectively evaluated sputum samples analyzed for M. tuberculosis complex at the International Reference Laboratory of Mycobacteriology, Copenhagen, Denmark in 2002-2011. We selected culture-confirmed tuberculosis cases with ≥3 samples within 14 days before or after the initial culture-positive sample. We repeated the process for those with ≥2 samples within 28 days. The primary outcome was PCR-negative, smear-positive patients.
  
  
  RESULTS
  We included 53 533 sputum samples from 20 928 individuals; 1636 had culture-confirmed tuberculosis. Of these, 856 had ≥3 sputum samples analyzed within the 28 days, and 482 had ≥1 PCR result. Nine patients (2.5% of smear-positive patients) were smear positive/PCR negative; 8 of the 9 had a smear-positive result in only 1 of 3 samples, and 5 had a low smear grade. Of 722 patients with 2 samples, 7 (1.3% of smear-positive patients) were smear positive/PCR negative. Overall, none were smear positive for the sample that produced the negative PCR result.
  
  
  CONCLUSIONS
  Primary PCR identified >97% of serial smear-positive cases. The majority of the missed cases had low-grade smears. Nevertheless, the occurrence of smear-positive/PCR-negative cases underlines the importance of increasing the quantity and quality of samples. Moreover, it is important that samples analyzed with PCR are cultured, owing to higher-sensitivity drug susceptibility testing, differential diagnosis, and surveillance.
authors.affiliation: Departments of Respiratory Diseases and Allergy.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fløe
authors.affiliation: Departments of Respiratory Diseases and Allergy.
authors.forename: Ole
authors.initials: O
authors.lastname: Hilberg
authors.affiliation: International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Vibeke Østergaard
authors.initials: VØ
authors.lastname: Thomsen
authors.affiliation: International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Troels
authors.initials: T
authors.lastname: Lillebaek
authors.affiliation: Infectious Diseases, Aarhus University Hospital GloHAU Center for Global Health, Department of Public Health, Aarhus University.
authors.forename: Christian
authors.initials: C
authors.lastname: Wejse
mesh_terms: D000328:Adult; D000368:Aged; D001431:Bacteriological Techniques / Q000379:methods*; D003430:Cross-Sectional Studies; D003718:Denmark; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009161:Mycobacterium / Q000235:genetics / Q000302:isolation & purification*; D010356:Patient Isolation; D016133:Polymerase Chain Reaction / Q000379:methods*; D012189:Retrospective Studies; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*
keywords: in-hospital transmission; nucleic acid amplification; polymerase chain reaction; respiratory isolation; tuberculosis