Mortality among tuberculosis patients with acquired resistance to second-line antituberculosis drugs--United States, 1993-2008.

Abstract

Resistance to second-line antituberculosis drugs (SLDs) severely compromises treatment options of drug-resistant tuberculosis. We assessed the association between acquisition of resistance (AR) to second-line injectable drugs (SLIs) or fluoroquinolones (FQs) and mortality among tuberculosis cases confirmed by positive culture results with available initial and final drug susceptibility test (DST) results. We analyzed data from the US National Tuberculosis Surveillance System, 1993-2008. Acquired resistance was defined as drug susceptibility at initial DST but resistance to the same drug at final DST. We compared survival with Kaplan-Meier curves and analyzed the association between AR and mortality using a univariate extended Cox proportional hazards model adjusted for age. Of 2329 cases with both initial and final DSTs to SLIs, 49 (2.1%) acquired resistance; 13 of 49 (26.5%) had treatment terminated by death compared with 222 (10.0%) of those without AR to SLIs (P < .001). Of 1187 cases with both initial and final DSTs to FQs, 32 (2.8%) acquired resistance; 12 of 32 (37.5%) had treatment terminated by death compared with 121 (10.9%) of those without AR to FQs (P = .001). Controlling for age, mortality was significantly greater among cases with AR to SLDs than among cases without AR (adjusted hazard ratio [aHR] for SLIs: 2.8; 95% confidence interval [CI],1.4-5.4; aHR for FQ: 1.9; 95% CI, 1.0-3.5). Multidrug-resistant tuberculosis at treatment initiation, positive human immunodeficiency virus status, and extrapulmonary disease were also significantly associated with mortality. Mortality was significantly greater among tuberculosis cases with AR to SLDs. Providers should consider AR to SLDs early in treatment, monitor DST results, and avoid premature deaths.