title: Frequency and implications of pyrazinamide resistance in managing previously treated tuberculosis patients.
abstract: OBJECTIVE
  To determine the extent of pyrazinamide (PZA) resistance in isolates from previously treated patients from the Western Cape, South Africa.
  
  
  METHODS
  Drug-resistant isolates, isolates resistant to one or more drugs other than PZA (PZA resistance is not routinely determined) (n = 127), and drug-susceptible (n = 47) clinical isolates of Mycobacterium tuberculosis from previously treated patients from the Western Cape were phenotypically (BACTEC MGIT 960) and genotypically (pncA gene sequencing) analysed for PZA resistance.
  
  
  RESULTS
  MGIT analysis found that 68 of the 127 drug-resistant isolates were PZA-resistant. Nearly all (63/68) PZA-resistant isolates had diverse nucleotide changes scattered throughout the pncA gene, and five PZA-resistant isolates had no pncA mutations. Of the 47 phenotypically susceptible isolates, 46 were susceptible to PZA, while one isolate was PZA-monoresistant (OR = 53.0, 95% CI = 7.1-396.5). A pncA polymorphism (Thr114Met) that did not confer PZA resistance was also identified. PZA resistance was strongly associated with multidrug-resistant tuberculosis (MDR-TB).
  
  
  CONCLUSIONS
  An alarmingly high proportion of South African drug-resistant M. tuberculosis isolates are PZA-resistant, indicating that PZA should not be relied upon in managing patients with MDR-TB in the Western Cape. A method for the rapid detection of PZA resistance would be beneficial in managing patients with suspected drug resistance.
authors.affiliation: Department of Biomedical Sciences, Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors.forename: G E
authors.initials: GE
authors.lastname: Louw
authors.forename: R M
authors.initials: RM
authors.lastname: Warren
authors.forename: P R
authors.initials: PR
authors.lastname: Donald
authors.forename: M B
authors.initials: MB
authors.lastname: Murray
authors.forename: M
authors.initials: M
authors.lastname: Bosman
authors.forename: P D
authors.initials: PD
authors.lastname: Van Helden
authors.forename: D B
authors.initials: DB
authors.lastname: Young
authors.forename: T C
authors.initials: TC
authors.lastname: Victor
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001483:Base Sequence; D017931:DNA Primers; D004352:Drug Resistance, Microbial / Q000235:genetics; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics; D016133:Polymerase Chain Reaction; D011718:Pyrazinamide / Q000494:pharmacology / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D017931:DNA Primers; D011718:Pyrazinamide