Pyrazinamide resistance in Swedish multidrug-resistant tuberculosis 2003–2013

AbstractAims and objectivesThe aim of this study is to determine the prevalence of pyrazinamide (PZA) resistance among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains isolated in Sweden between 2003 and 2013 and to study the correlation between phenotypic PZA susceptibility testing and the presence of pncA mutations.MethodsA total of 117 clinical TB isolates defined as MDR were tested for PZA resistance in the Bactec MGIT 960 system and subsequently screened for mutations within the pncA gene using Sanger sequencing.ResultsPZA is a first-line key drug in the treatment of TB, including MDR-TB susceptible to PZA, and the phenotypic test showed that 53% of the MDR isolates from Sweden were PZA resistant. Preliminary sequencing results show that 95% of the PZA-resistant strains had a mutation in the pncA gene or its putative promoter. Of the PZA-susceptible strains, 73% had a wild type pncA, a proportion which increases to 89% if the silent mutation Ser65Ser (TCC65TCT) is included in this group. Moreover, the sensitivity and specificity of pncA sequencing, using the Bactec MGIT 960 system as the gold standard, was determined to be 95% and 89%, respectively. The results also showed an increase of PZA resistance among the Swedish MDR isolates during the studied period. Between 2003 and 2008, the prevalence of PZA resistance was 44% (n=48), while in the latter period (2009–2013) the prevalence had increased to 59% (n=69). No major difference in PZA resistance was seen among MDR patients of various geographical origins.ConclusionsThe results from the last 11-year period demonstrate an increase of PZA resistance among Swedish MDR cases. Additionally, the detection of pncA gene mutations, or their absence, was confirmed as a useful method for predicting PZA resistance