title: Impact of second-line drug resistance on tuberculosis treatment outcomes in the United States: MDR-TB is bad enough.
abstract: METHODS
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These results suggest that the effect of rifamycin resistance may outweigh the more  modest effects of resistance to specific SLDs.
authors.affiliation: Division of Tuberculosis Elimination, US Centers for Disease Control and Prevention, Atlanta, GA, USA. SAlthomsons@cdc.gov
authors.forename: S P
authors.initials: SP
authors.lastname: Althomsons
authors.forename: J P
authors.initials: JP
authors.lastname: Cegielski
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011159:Population Surveillance / Q000379:methods*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D000995:Antitubercular Agents