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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Division of Tuberculosis Elimination, International Research and Programs Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
Julia V
JV
Ershova
Division of Tuberculosis Elimination, International Research and Programs Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
Ekaterina V
EV
Kurbatova
Division of Tuberculosis Elimination, International Research and Programs Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
Patrick K
PK
Moonan
Division of Tuberculosis Elimination, International Research and Programs Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
J Peter
JP
Cegielski
D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D005260:Female; D006678:HIV; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D016019:Survival Analysis; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology* / Q000401:mortality*; D014481:United States / Q000453:epidemiology
D000995:Antitubercular Agents
acquired drug resistance; tuberculosis