Precision Rifampin Trial for Personalized Dosing

Inclusion Criteria: 1. Age 3 or older 2. Diagnosed with active, rifampin-susceptible, pulmonary TB- sputum positive for M. tuberculosis complex without rpoB mutation, or culture for M. tuberculosis with conventional rifampin susceptibility OR among children unable to expectorate, meeting confirmed or probable consensus clinical case definitions for intrathoracic childhood TB 3. Initiating combination anti-TB therapy with isoniazid, rifampin, pyrazinamide, and ethambutol 4. Subject or guardian is able to provide informed consent; and for children 7 years or older, provide assent 5. Stated willingness to comply with all trial procedures and availability for the duration of the trial 6. Resident within a pre-defined geographic area to ensure TB clinic follow-up Exclusion Criteria: 1. Urinary incontinence: may complicate urine collection 2. Oliguria: may complicate urine collection and limit correlation of urinary excretion and serum concentrations 3. Kidney disease, defined as a glomerular filtration rate (GFR) \< 60 mL/min: In 5R01 AI137080, those adults with GFR \< 60 mL/min had reduced correlation or urinary rifampin excretion and serum concentrations. 4. Severe anemia, defined as a hemoglobin level less than 7 g/dL: given planned phlebotomy 5. Elevated liver function tests, defined as DAIDS grade 3 or above (ALT or AST \>/= 5 x upper limit of normal): may confound potential toxicity signals of dose adjustment strategy 6. Pregnancy: Urine rifampin spectrophotometry has not been studied in pregnant people, higher dose rifampin also less studied in pregnancy, and may confound potential toxicity signals (e.g. elevated liver function tests in pregnancy). Urine pregnancy test will be completed at screening in people of child-bearing potential. Child-bearing potential is defined as a person able to menstruate (menstruation in the last 12 months) and not receiving a form of contraception with less than \<1% failure rate (oral levonorgestrel, IUD or etonogestrel implant). 7. Weight \<10.0 kg (dose increase may exceed 30mg/kg/dose) 8. Current treatment with a drug known to have significant interaction with anti-TB therapy 9. Excessive alcohol use? (for example, Men consuming \> 14 standardized drinks per week and/or \> 4 drinks per day OR women consuming \>7 standardized drinks per week, and/or \>3 drinks per day, or at the discretion of the investigator(s).