Background: The aim of this study was to investigate the rates of pyrazinamide (PZA) resistance and the associated risk factors as well as to evaluate the pncA gene loci as a marker for PZA resistance in China.

Method: A population-based multi-center study of pulmonary TB cases was carried out from 2011 to 2013 in four Chinese district/counties with different geographic and socio-economic features. Testing for multidrug-resistant tuberculosis (MDR-TB) and susceptibility to PZA were determined by the proportion method on Löwenstein-Jensen medium and BACTEC MGIT 960 respectively. Mutations in the pncA gene were identified by sequencing.

Results: Among 878 culture positive cases, 147(16.7%) were resistant to PZA, with a significantly higher proportion among MDR isolates compared to the drug sensitive isolates (30.2% VS 7.7%, p<0.001). Totally, 136 isolates had a non-synonymous pncA mutation, with a comparable diagnostic performance between Beijing family and non-Beijing family as well as between MDR-TB and 1st-line drug susceptible TB. Furthermore, the mutations in isolates with high-level PZA resistance (MIC>500mg/L) were observed mainly in three regions of the pncA gene (codon 51-76, codon 130-142 and codon 163-180). Patients with prior treatment history had a significantly higher risk for PZA mono-resistance (OR:2.86,95%CI:1.363-6.015) and MDR PZA resistance (OR:6.47, 95%CI:3.186-13.15), while the additional factors associated with MDR-PZA resistance were the patient's age (OR:1.02, 95%CI:1.003-1.042), lung cavity (OR:2.64, 95%CI:1.296-5.391).

Conclusions: These findings suggest that it is a priority to identify PZA resistance in MDR-TB and a rapid molecular diagnostic test based on pncA mutations in the Chinese settings where MDR-TB prevalence is high should be developed.