ABSTRACTPyrazinamide (PZA) has important sterilizing activity in tuberculosis (TB) chemotherapy. We describe trends, risk factors, and molecular epidemiology associated with PZA-resistant (PZAr)Mycobacterium tuberculosisin New York City (NYC). From 2001 to 2008, all incident culture-positive TB cases reported by the NYC Department of Health and Mental Hygiene (DOHMH) were genotyped by IS6110-based restriction fragment length polymorphism and spoligotype. Multidrug-resistant (MDR) isolates underwent DNA sequencing of resistance-determining regions ofpncA,rpoB,katG, andfabG1. Demographic and clinical information were extracted from the NYC DOHMH TB registry. During this period, PZArdoubled (1.6% to 3.6%) overall, accounting for 44% (70/159) of the MDR population and 1.4% (75/5511) of the non-MDR population. Molecular genotyping revealed strong microbial phylogenetic associations with PZAr. Clustered isolates and those from acid-fast bacillus (AFB) smear-positive cases had 2.7 (95% confidence interval [CI] = 1.71 to 4.36) and 2.0 (95% CI = 1.19 to 3.43) times higher odds of being PZAr, respectively, indicating a strong likelihood of recent transmission. Among the MDR population, PZArwas acquired somewhat more frequently via primary transmission than by independent pathways. Our molecular analysis also revealed that several historicM. tuberculosisstrains responsible for MDR TB outbreaks in the early 1990s were continuing to circulate in NYC. We conclude that the increasing incidence of PZAr, with clear microbial risk factors, underscores the importance of routine PZA drug susceptibility testing andM. tuberculosisgenotyping for the identification, control, and prevention of increasingly resistant organisms.
Characterization by automated DNA sequencing of mutations in the gene (rpoB) encoding the RNA polymerase beta subunit in rifampin-resistant Mycobacterium tuberculosis strains from New York City and Texas.
