title: Epidemiologic Correlates of Pyrazinamide-Resistant Mycobacterium tuberculosis in New York City.
abstract: 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 in 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 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 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 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 M. tuberculosis strains responsible for MDR TB 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 M. tuberculosis genotyping for the identification, control, and prevention of increasingly resistant organisms.
authors.affiliation: Public Health Research Institute, Rutgers University, Newark, New Jersey, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Verdugo
authors.affiliation: Public Health Research Institute, Rutgers University, Newark, New Jersey, USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Fallows
authors.affiliation: Bureau of Tuberculosis Control, New York City Department of Health and Mental Hygiene, Long Island City, New York, USA.
authors.forename: Shama
authors.initials: S
authors.lastname: Ahuja
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Schluger
authors.affiliation: Public Health Research Institute, Rutgers University, Newark, New Jersey, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Kreiswirth
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA bm2055@columbia.edu.
authors.forename: Barun
authors.initials: B
authors.lastname: Mathema
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity; D009519:New York City / Q000453:epidemiology; D011718:Pyrazinamide / Q000627:therapeutic use*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000453:epidemiology*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide