title: Proficiency of drug susceptibility testing of Mycobacterium tuberculosis against pyrazinamide: the Swedish experience.
abstract: BACKGROUND
  Pyrazinamide (PZA) is a key drug in the treatment of tuberculosis (TB), including multidrug-resistant TB. Drug susceptibility testing (DST) of Mycobacterium tuberculosis against PZA is not included in the World Health Organization's yearly proficiency testing. There is an increasing need to establish quality control of PZA DST.
  
  
  OBJECTIVE
  To evaluate the performance of PZA DST and to introduce a quality assurance system for the test in Sweden.
  
  
  METHODS
  Panels with PZA-susceptible and -resistant isolates were used in three rounds of proficiency testing in all five Swedish clinical TB laboratories and our reference laboratory. All laboratories used the MGIT 960 system. Minimum inhibitory concentrations (MICs) were determined and the pncA gene was sequenced to further characterise the 52 panel strains.
  
  
  RESULTS
  Good agreement was seen between the phenotypic PZA DST and pncA sequence data, and MIC determination confirmed high levels of resistance. However, in contrast to other drugs, for which correct proficiency test results were observed, specificity problems occurred for PZA DST in some laboratories.
  
  
  CONCLUSIONS
  In Sweden, using panel testing, differences were seen in the proficiency of TB laboratories in correctly identifying PZA susceptibility. Improved results were noted in the third round; PZA has therefore been included in yearly proficiency testing.
authors.affiliation: Department of Preparedness, Swedish Institute for Communicable Disease Control, Solna, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Hoffner
authors.forename: K
authors.initials: K
authors.lastname: Angeby
authors.forename: E
authors.initials: E
authors.lastname: Sturegård
authors.forename: B
authors.initials: B
authors.lastname: Jönsson
authors.forename: A
authors.initials: A
authors.lastname: Johansson
authors.forename: M
authors.initials: M
authors.lastname: Sellin
authors.forename: J
authors.initials: J
authors.lastname: Werngren
mesh_terms: D000581:Amidohydrolases / Q000235:genetics; D000995:Antitubercular Agents / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D006801:Humans; D059021:Laboratory Proficiency Testing / Q000592:standards*; D008826:Microbial Sensitivity Tests / Q000592:standards*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D015588:Observer Variation; D011237:Predictive Value of Tests; D011718:Pyrazinamide / Q000627:therapeutic use*; D011786:Quality Control; D019984:Quality Indicators, Health Care / Q000592:standards*; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D013548:Sweden; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D000581:Amidohydrolases; C487496:PncA protein, Mycobacterium tuberculosis