Epidemiologic correlates of pyrazinamide resistant Mycobacterium tuberculosis in New York City.
Antimicrob Agents Chemother. 2015 Jul 20;
Authors: Verdugo D, Fallows D, Ahuja S, Schluger N, Kreiswirth B, Mathema B
Pyrazinamide (PZA) has important sterilizing activity in tuberculosis (TB) chemotherapy. We describe trends, risk factors and molecular epidemiology associated with PZA resistant (PZA(R)) Mycobacterium tuberculosis (Mtb) in New York City (NYC). From 2001-2008, all incident culture-positive TB cases reported by 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 of pncA, rpoB, katG and fabG1. Demographic and clinical information were extracted from the NYC DOHMH TB Registry. During this period, PZA(R) doubled (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 PZA(R). Clustered isolates and those from AFB smear positive cases had 2.7 (95% CI=1.71-4.36) and 2.0 (95% CI=1.19-3.43) times higher odds of being PZA(R), respectively, indicating a strong likelihood of recent transmission. Among the MDR population, PZA(R) was acquired somewhat more frequently via primary transmission than by independent pathways. Our molecular analysis also revealed that several historic Mtb strains responsible for MDR outbreaks in the early 1990s were continuing to circulate in NYC. We conclude that the increasing incidence of PZA(R), with clear microbial risk factors, underscores the importance of routine PZA drug susceptibility testing and Mtb genotyping for the identification, control and prevention of increasingly resistant organisms.
PMID: 26195530 [PubMed - as supplied by publisher]