Assessing PA-824 for Tuberculosis (the APT Trial)

Inclusion Criteria: 1. Suspected pulmonary tuberculosis with acid-fast bacilli in a stained smear of expectorated sputum or Gene Xpert positive sputum sample. Patients having extra-pulmonary manifestations of tuberculosis, in addition to smear-positive pulmonary disease, are eligible for enrollment. 2. Age \> 18 years 3. . Weight ≥ 40 kg and ≤ 80 kg 4. Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs) 5. . Signed informed consent 6. . HIV negative, or positive with CD4 ≥350 cells/cu mm and not currently taking or planning to take combination antiretroviral therapy for HIV during the study. 7. Ability to adhere with study follow-up 8 Agrees to adhere to contraceptive requirements \- Exclusion Criteria: 1. Pregnant or breast-feeding 2. Known intolerance or allergy to any of the study drugs 3. Concomitant disorders or conditions for which isoniazid, rifampin, rifabutin, pyrazinamide, or ethambutol is contraindicated. These include severe hepatic damage, acute liver disease of any cause, allergy to the drug, and acute uncontrolled gouty arthritis. 4. Current or planned therapy, during the intensive phase of TB therapy with cyclosporine or tacrolimus, which have unacceptable interactions with rifamycins. 5. Any medical or psychosocial condition, which, in the view of the study investigator, makes study participation inadvisable. 6. Pulmonary silicosis 7. Central nervous system TB 8. ECG at screening with corrected QT interval (QTc) (Fridericia correction) interval \>450 ms or any clinically-significant, in the opinion of the investigator, ECG abnormality 9. History and/or presence (or evidence) of neuropathy or epilepsy. 10. History of lens opacity or evidence of lens opacity on slit lamp ophthalmologic examination with a value of 1.0 or higher on age-related eye disease scale 2 (AREDS2) Clinical Lens Opacity Classification and Grading System scale. 11. Infection with an isolate known to be resistant to a first-line TB drug (for example, patients with Gene Xpert screening through the local TB program with results suggesting resistance to rifampin) 12. Laboratory parameters done at, or 14 days prior to, screening (with results available for review by study personnel) demonstrating any of the following: * Serum alanine aminotransferase (ALT) activity \> 3 times the upper limit of normal * Serum total bilirubin level \> 2 times the upper limit of normal * Serum creatinine greater than the upper limit of normal * Hemoglobin level less than 7.0 g/dL * Platelet count less than 100,000/mm3 * Positive pregnancy test (women of childbearing potential) 13. More than five days of treatment directed against active tuberculosis in the past 6 months -