Tuberculosis is a leading global cause of morbidity and mortality. Even if cured, most patients are left with permanent lung damage that impairs lung function and shortens long-term survival. These concerns are increased many-fold in rifampin-resistant (RIF-R) TB, in which cure is less likely, and long-term outcomes are more profoundly affected. This project will develop the first regimen meeting WHO criteria for a pan-TB indication, ie, without requiring knowledge of RIF susceptibility. The regimen will combine sutezolid (a linezolid analog with a superior therapeutic index and safety profile in phase 1 and 2 trials) with the approved anti-TB drugs bedaquiline and pretomanid. This phase 2c trial will test sutezolid at 2 dose levels to optimize its efficacy and safety. It will also test whether the addition of N-acetylcysteine (NAC), a re-purposed host-directed WHO essential medicine, can protect the lung and liver against oxidative damage, preserve lung function, and accelerate the eradication of MTB infection by replenishing glutathione (GSH). Our modelling indicates this new regimen (SBPN) can be a highly effective intervention, preventing deaths due to treatment failure in patients with RIF-R-TB, and recovering years of life otherwise lost post-TB in all patients by preserving lung function. The project will be conducted by a consortium of public, non-profit, and private interests that bring unique knowledge, expertise, and capabilities.