Phenotypic and genotypic characterization of pyrazinamide resistance among multidrug-resistant Mycobacterium tuberculosis clinical isolates in Hangzhou, China

摘要

ObjectivesPyrazinamide (PZA) is a crucial first-line tuberculosis (TB) drug recommended for both drug-susceptible and multidrug-resistantMycobacterium tuberculosis.This study aimed to evaluate the performance of the sequencing method ofpncA, rpsAandpanDmutations in detecting PZA resistance in multidrug-resistant (MDR) TB isolates. MethodsWe sequenced thepncA, rpsAandpanDgenes and performed PZA susceptibility tests across 291 MDR-TB isolates to evaluate the performance of the sequencing method of these genes in detecting PZA resistance. ResultsResults showed that 145 (90.0%) of 161 PZA phenotypic resistant isolates had mutations inpncA.Among the 16 isolates (10.0%) which did not have mutations inpncA,ten and three isolates had mutations inrpsAandpanD,respectively. The sequencing method for detecting mutations inpncAalone had 90.1% (95% confidence interval (CI), 84.4–94.2) sensitivity and 92.3% (95% CI, 86.3–96.3) specificity. The combination of all three genes increased the sensitivity from 90.1% (95% CI, 84.4–94.2) to 98.1% (95% CI, 94.7–99.6) (p?