Patient description: Patient A is a 30-year-old male who was admitted to the hospital after 10 days of cough, profuse nocturnal sweating and loss of appetite. He had traveled to India 1 months ago and has not any positive history of TB vaccination. He is a previously healthy man, working as an engineer in a high tech company. He doesn't smoke o use any illicit drugs. He was febrile (38 c) with heart rate of 115 b/min, respiratory rate of 22, BP of 125/75 mmHg and O2 sat of 97%. Chest X-ray showed infiltrate in the middle of left lung with diameter of 1.8 cm with signs of cavitation. The sputum smear revealed positive sputum culture for Mycobacterium tuberculosis which are sensitive of the first-line TB drugs (isoniazid, streptomycin, rifampicin and ethambutol). Lab study is reported bellow: Hgb: 13 g/dl WBC: 14000 /mm3 Plt: 300000 /ml AST: 13 U/L ALT: 15 U/L Alk P: 53 U/L Bill total: 0.6 mg/dl Na: 137 mEq/l K: 4 mEq/l Creatinine: 0.5 mg/dl BUN: 10 mg/dl ESR: 120 mm/hr

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Tuberculosis Culture-confirmed pulmonary or extrapulmonary tuberculosis due to a strain of M tuberculosis sensitive to rifampin, ethambutol and pyrazinamide based upon specimens (sputum or other pulmonary or extrapulmonary disease site specimens) collected no more than 8 weeks before and no more than 2 weeks after the start of the initial therapy. Susceptibility testing results documenting susceptibility to rifampin and ethambutol must be available at the time of enrollment. Susceptibility results to pyrazinamide may be pending at enrollment as long as pyrazinamide resistance is not known to be present based on prior testing. If pyrazinamide resistance is detected and confirmed (see Study Definitions) the patient will be withdrawn from the study therapy, treatment continued as recommended by the treating physician, and follow-up continued as per the protocol. 2. Decision to discontinue or not use isoniazid for one or both of these following conditions within the first 70 days of therapy Isoniazid resistant strain (growth in 0.2 mcg/ml or 0.1 mcg/ml of isoniazid on solid or liquid media, respectively) The discontinuation of isoniazid due to intolerance (as judged by the principal investigator see Study Definitions) 3. For patients enrolled after the start of therapy, documentation of adequate initial regimen as recommended in the CDC/ATS Treatment Guidelines (Appendix 1) is required. There are two means by which this requirement can be met The standard 4-drug regimen of isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin or both The same regimen with isoniazid excluded for some or all doses in patients with known isoniazid intolerance or tuberculosis due to an isoniazid-resistant strain (i.e., the 3-drug regimen of rifampin, pyrazinamide and either ethambutol or streptomycin or both) 4. A minimum duration of daily treatment as defined by one of two methods daily doses within 17 days (with at least 10 of the 14 doses directly observed) directly observed doses within 23 days Following the minimum daily phase of therapy, adequate pre-enrollment treatment is defined as directly administered therapy given daily, twice weekly, or thrice weekly using CDC/ATS guidelines. Documenting pre-enrollment therapy is accomplished by hospital medical records and/or clinic entries of DOT. 5. Age: 18 years or older 6. Documentation of negative test for human immunodeficiency virus (HIV) infection. Documentation means written copies of HIV laboratory test results. A negative HIV test result within the 6 months prior to enrollment is acceptable. 7. Documentation of study baseline laboratory parameters. Baseline laboratory parameters obtained no more than 2 weeks prior to enrollment and must be within the following limits: 1. . Amino aspartate transferase (AST) activity less than 3 times upper limit of normal; 2. . Total bilirubin level less than 2.5 times upper limit of normal; 3. . Creatinine level less than 2 times upper limit of normal; 4. . Hemoglobin level of at least 7.0 g/dL; 5. . Platelet count of at least 50,000 mm3 8. Karnofsky score of at least 60. See Appendix 6 for Karnofsky scoring system. 9. A negative pregnancy test within the past 14 days for women with child-bearing potential, and a willingness to practice an adequate (preferably barrier) method of birth control. In addition, women with child-bearing potential should be offered information concerning sources of contraceptive counseling and services. 10. Informed consent signed by patient and investigator documenting the willingness to use the 3-drug, intermittent regimen is required, in accordance with state law and local IRB requirements. Patients who are unable to provide informed consent due to an inability to comprehend English may be enrolled by providing informed consent by either of two means the use of a translator to provide a verbal translation of the IRB-approved English version of the consent form; the translator will sign the English form attesting the translation and the patient will sign the IRB-approved translation of the short form the use of a translated consent document, approved by the IRB, that is in the patient's native language  Patients with known treatment-limiting reaction to rifamycins, pyrazinamide, or ethambutol. 2. Diagnosis of silicotuberculosis or tuberculosis of the central nervous system 3. Patients who, during initial therapy with CDC/ATS recommended therapy with isoniazid, rifampin and pyrazinamide plus either ethambutol or streptomycin or both, have received greater than 21 days of treatment with additional drugs with known antituberculosis activity see Concomitant Medications During Study Phase Therapy. 4. Patients with isoniazid intolerance or isoniazid-resistant tuberculosis who during pre-enrollment therapy have missed a total of two weeks of directly observed therapy doses due to non-compliance. 5. Patients enrolled due to isoniazid intolerance who during pre-enrollment therapy have missed a total of over 4 weeks of directly observed therapy doses for management of drug intolerance