Acquired Resistance to Second-Line Drugs Among Persons With Tuberculosis in the United States

Abstract

Acquired resistance to second-line drugs (SLDs) is a problem in treating patients with drug-resistant tuberculosis worldwide. The objectives of this study were to identify risk factors for acquired resistance (AR) to injectable SLDs (INJ SLDs) and fluoroquinolones in the US National tuberculosis Surveillance System, 1993-2008. We selected cases for which the initial and final drug susceptibility test (DST) results had been reported. We defined AR as resistance at the final DST but susceptibility to the same drug at the initial DST. We analyzed AR using 2-way frequency tables and multivariable logistic regression. The baseline prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis was 12.6% (1864/14 770) and 0.38% (56/14 770), respectively. Of 2274 individuals without initial resistance to INJ SLDs, 49 (2.2%) acquired resistance. Of 1141 initially susceptible to fluoroquinolones, 32 (2.8%) acquired resistance. The AR to INJ SLDs was associated with age group 25-44 years (adjusted odds ratio [aOR], 2.7; 95% confidence interval [CI], 1.2-6.3), positive HIV (human immunodeficiency virus) status (aOR, 2.5; 95% CI, 1.3-4.7), MDR at treatment initiation (aOR, 5.5; 95% CI, 2.9-10.5), and treatment with any SLD (aOR, 2.4; 95% CI,1.2-4.7). The AR to fluoroquinolones was associated with MDR tuberculosis at treatment initiation (aOR, 6.5; 95% CI, 2.9-14.6). Among patients with initial and final DST reported, the risk factors for AR to INJ SLDs included age, positive HIV status, MDR tuberculosis and initial treatment with any SLD, while the only predictor for AR to fluoroquinolones was MDR tuberculosis at treatment initiation. Providers should consider monitoring SLD DST for MDR tuberculosis patients in the indicated subgroups.