23840002

PMC4578633

CC999999/Intramural CDC HHS/United States

CDC Public Access

Introduction

Pyrazinamide (PZA) is essential in tuberculosis (TB) treatment. We describe the prevalence, trends and predictors of PZA resistance in Mycobacterium tuberculosis complex (MTBC) in the U.S.

Methods

We analyzed culture-positive MTBC cases with reported drug susceptibility tests (DST) for PZA in 38 jurisdictions routinely testing for PZA susceptibility from 1999-2009. National TB Genotyping Service data for 2004-2009 were used to distinguish Mycobacterium tuberculosis from Mycobacterium bovis and determine phylogenetic lineage.

Results

Overall 2.7% (2,167/79,321) of MTBC cases had PZA resistance, increasing annually from 2.0% to 3.3% during 1999-2009 (P<0.001), largely due to an increase in PZA monoresistance. PZA-monoresistant MTBC (versus drug-susceptible) was associated with age 0-24 years (adjusted prevalence ratio [aPR]=1.50, 95% CI 1.31-1.71), Hispanic ethnicity (aPR=3.52, 2.96-4.18), HIV infection (aPR=1.43, 1.15-1.77), extrapulmonary disease (aPR=3.02, 2.60-3.52), and normal chest radiograph (aPR=1.88, 1.63-2.16), and inversely associated with Asian (aPR=0.59, 0.47-0.73) and Black (aPR=0.37, 0.29-0.49) race. Among multidrug-resistant (MDR) cases 38.0% were PZA-resistant; PZA resistance in MDR MTBC was associated with female sex (aPR=1.25, 1.08-1.46) and previous TB diagnosis (aPR=1.37, 1.16-1.62). Of 28,080 cases with genotyping data, 925 (3.3%) had PZA resistance; 465/925 (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% versus 0.9%; respectively; aPR=2.26, 1.53-3.36), but in MDR cases it was lower in the Indo-Oceanic lineage (22.0% versus 43.4%, respectively; aPR=0.54, 0.32-0.90).

Conclusions

Specific human and mycobacterial characteristics were associated with pyrazinamide-resistant MTBC, reflecting both specific subgroups of the population and phylogenetic lineages of the mycobacteria.