Treatment Regimen for Tuberculosis Clinical Trials

Standard First-Line Treatment Regimen

The American Thoracic Society recommends a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months, followed by isoniazid and rifampin for an additional 4 months 1, 2
Initial phase (first 2 months): Daily isoniazid, rifampin, pyrazinamide, and ethambutol 1
Continuation phase (next 4 months): Daily isoniazid and rifampin 1
The recommended time frame is to administer all doses for the intensive phase within 3 months and those for the continuation phase within 6 months, so that the 6-month regimen is completed within 9 months 1

Daily dosing throughout treatment is preferred 1
Thrice-weekly dosing in the continuation phase is acceptable (strong recommendation; moderate certainty in evidence) 1
If intermittent therapy is used in the continuation phase, thrice-weekly is suggested over twice-weekly therapy (conditional recommendation) 1
Once-weekly therapy with INH 900 mg and rifapentine 600 mg in the continuation phase is not recommended (strong recommendation) 1

If interruption is <14 days during intensive phase: Continue treatment to complete planned total number of doses (within 3 months) 1
If interruption is ≥14 days during intensive phase: Restart treatment from the beginning 1
If interruption occurs during continuation phase with ≥80% of doses completed and initial sputum was AFB smear negative: Continue therapy until all doses are completed 1
If interruption occurs during continuation phase with <80% of doses completed and lapse is ≥3 months: Restart therapy from the beginning 1

For Isoniazid-Resistant TB: Add a later-generation fluoroquinolone to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide 3
For MDR-TB Clinical Trials: Include at least five drugs in the intensive phase and four drugs in the continuation phase 4
For MDR-TB Clinical Trials: Include a later-generation fluoroquinolone (levofloxacin or moxifloxacin) (strong recommendation) 4
For MDR-TB Clinical Trials: Include bedaquiline (strong recommendation) 4
For MDR-TB Clinical Trials: Consider including linezolid, clofazimine, and cycloserine (conditional recommendations) 4
For MDR-TB Clinical Trials: Suggested intensive phase duration: 5-7 months after culture conversion 4
For MDR-TB Clinical Trials: Suggested total treatment duration: 15-21 months after culture conversion 4

Regular clinical assessment for symptom improvement 5
Directly observed therapy (DOT) is strongly recommended to ensure adherence 5, 6
Sputum cultures should be obtained monthly until conversion, then less frequently 1
Drug susceptibility testing should be performed on the first isolate from all patients 7

Never add a single drug to a failing regimen as this leads to acquired resistance 7
Adherence to the full regimen is critical to prevent relapse and development of drug resistance 6