title: Epidemiology of pyrazinamide-resistant tuberculosis in the United States, 1999-2009.
abstract: BACKGROUND
  Pyrazinamide (PZA) is essential in tuberculosis treatment. We describe the prevalence, trends, and predictors of PZA resistance in Mycobacterium tuberculosis complex (MTBC) in the United States.
  
  
  METHODS
  We analyzed culture-positive MTBC cases with reported drug susceptibility tests for PZA in 38 jurisdictions routinely testing for PZA susceptibility from 1999 to 2009. National Tuberculosis Genotyping Service data for 2004-2009 were used to distinguish M. tuberculosis from Mycobacterium bovis and determine phylogenetic lineage.
  
  
  RESULTS
  Overall 2.7% (2167/79 321) of MTBC cases had PZA resistance, increasing annually from 2.0% to 3.3% during 1999-2009 (P < .001), largely because of an increase in PZA monoresistance. PZA-monoresistant MTBC (vs drug-susceptible) was associated with an age of 0-24 years (adjusted prevalence ratio [aPR],1.50; 95% confidence interval [CI], 1.31-1.71), Hispanic ethnicity (aPR, 3.52; 95% CI, 2.96-4.18), human immunodeficiency virus infection (aPR, 1.43; 95% CI, 1.15-1.77), extrapulmonary disease (aPR, 3.02; 95% CI, 2.60-3.52), and normal chest radiograph (aPR, 1.88; 95% CI, 1.63-2.16) and was inversely associated with Asian (aPR, 0.59; 95% CI, .47-.73) and black (aPR, 0.37; 95% CI, .29-.49) race. Among multidrug-resistant (MDR) cases, 38.0% were PZA-resistant; PZA resistance in MDR MTBC was associated with female sex (aPR, 1.25; 95% CI, 1.08-1.46) and previous tuberculosis diagnosis (aPR, 1.37; 95% CI, 1.16-1.62). Of 28 080 cases with genotyping data, 925 (3.3%) had PZA resistance; 465 of 925 (50.3%) were M. bovis. In non-MDR M. tuberculosis cases, PZA resistance was higher in the Indo-Oceanic than the East Asian lineage (2.2% vs 0.9%, respectively; aPR, 2.26; 95% CI, 1.53-3.36), but in MDR cases it was lower in the Indo-Oceanic lineage (22.0% vs 43.4%, respectively; aPR, 0.54; 95% CI, .32-.90).
  
  
  CONCLUSIONS
  Specific human and mycobacterial characteristics were associated with PZA-resistant MTBC, reflecting both specific subgroups of the population and phylogenetic lineages of the mycobacteria.
authors.affiliation: Division of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Kurbatova
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Cavanaugh
authors.forename: Tracy
authors.initials: T
authors.lastname: Dalton
authors.forename: Eleanor S
authors.initials: ES
authors.lastname: Click
authors.forename: J Peter
authors.initials: JP
authors.lastname: Cegielski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D011718:Pyrazinamide / Q000494:pharmacology*; D012307:Risk Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology* / Q000382:microbiology*; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide
keywords: drug resistance; epidemiology; pyrazinamide; tuberculosis