Outcomes

The primary pharmacokinetic/pharmacodynamic (PK/PD) endpoint, AUC of rifampin in plasma at steady state divided by the MIC for 99.9% of M. tuberculosis (MIC_99.9), has been previously reported (36). The primary efficacy endpoint was the change in elimination rate of M. tuberculosis log₁₀ colony-forming units per milliliter in overnight pooled sputum samples collected throughout the intensive phase and cultured on 7H11 Middlebrook medium. Secondary efficacy endpoints included proportion of culture conversion in Löwenstein-Jensen (LJ) medium at 8 weeks, and proportion of unfavorable outcomes (treatment failure, recurrence after cure, or death) at 12 months. We classified recurrent disease by identical 24-locus mycobacterial interspersed repetitive units–variable number tandem repeat (MIRU-VNTR) sequencing as relapsed disease, and by nonidentical MIRU-VNTR as reinfection. The primary safety endpoint was the frequency of grade 2 or higher rifampin-related AEs, per the Division of Microbiology and Infectious Diseases (National Institute of Allergy and Infectious Diseases) Adult Toxicity Table (41), during the intensive phase and up to 4 weeks thereafter.