Impact of second-line drug resistance on tuberculosis treatment outcomes in the United States: MDR-TB is bad enough

SETTING: The worldwide emergence of extensively drug-resistant tuberculosis (TB) has focused attention on treatment with second-line drugs (SLDs).OBJECTIVE: To determine the impact on outcomes of resistance to individual SLDs, we analyzed successful treatment completion and death among drug-resistant TB cases in the US national TB surveillance system, 1993-2007 (N = 195 518).DESIGN: We defined four combinations of first-line drug (FLD) resistance based on isoniazid (INH) and rifamycin, and three patterns of SLD resistance: fluoroquinolones, injectable SLDs and other oral SLDs. We compared treatment outcomes of cases by FLD resistance, with and without each pattern of SLD resistance.RESULTS: In all but one instance, cases with FLD resistance but no SLD resistance had better outcomes than cases with SLD resistance. Rifamycin resistance, alone or with INH, resulted in a greater decline in treatment completion and greater increase in deaths than resistance to SLDs. Among patients with multidrug-resistant TB, additional resistance to injectable SLDs was statistically significant. Outcomes were better for human immunodeficiency virus (HIV) negative than HIV-positive cases for all resistance patterns, but improved among HIV-infected cases after 1998, when highly active antiretroviral treatment became widely available.CONCLUSION: These results suggest that the effect of rifamycin resistance may outweigh the more modest effects of resistance to specific SLDs.