Treatment Regimen for Tuberculosis
For drug-susceptible tuberculosis, administer a four-drug regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol daily for 2 months, followed by isoniazid and rifampin daily for 4 months, for a total duration of 6 months. 1
Standard Dosing Schedule
Initial Intensive Phase (2 months)
All four drugs must be administered together during this phase to maximize effectiveness and prevent drug resistance 1:
- Isoniazid: 5 mg/kg daily (maximum 300 mg/day) 2, 1
- Rifampin: 10 mg/kg daily; 450 mg if <50 kg, 600 mg if ≥50 kg 2, 1
- Pyrazinamide: 35 mg/kg daily for patients <50 kg; 2.0 g daily for patients ≥50 kg 2, 1
- Ethambutol: 15 mg/kg daily 2, 1
Continuation Phase (4 months)
After completing the intensive phase 2, 1:
- Isoniazid: 5 mg/kg daily (maximum 300 mg/day) 2
- Rifampin: 10 mg/kg daily; 450 mg if <50 kg, 600 mg if ≥50 kg 2
Frequency Options
Daily therapy is the standard approach, but alternative dosing schedules have proven highly effective 2:
- Daily throughout: Medications given 7 days per week for the entire 6-month course 2
- Daily for 2 months, then twice weekly for 4 months: Initial phase daily, continuation phase 2 times per week 2
- Three times weekly throughout: All medications given 3 times per week for 6 months 2
When using intermittent (twice or three times weekly) dosing, directly observed therapy (DOT) must be implemented 2, 3.
When to Omit the Fourth Drug
Ethambutol can be omitted only in previously untreated patients who are HIV-negative and are not contacts of drug-resistant cases 2. However, this is only appropriate when the local isoniazid resistance rate is ≤4% 1. Given the critical importance of preventing drug resistance, it is safer to include all four drugs in the initial phase for all patients 1.
Critical Treatment Modifications
Extension to 9 Months
Extend the continuation phase to 7 additional months (total 9 months) in the following situations 1:
- Cavitary pulmonary TB with positive sputum cultures after 2 months of treatment 1
- Initial treatment that did not include pyrazinamide 2
- HIV-positive patients with CD4+ counts <100 cells/mm³ 1
TB Meningitis or CNS Disease
Treat for 12 months total: 2 months of four-drug therapy (isoniazid, rifampin, pyrazinamide, ethambutol) followed by 10 months of isoniazid and rifampin 2.
Special Populations
HIV-Positive Patients
For patients with CD4+ counts <100 cells/mm³, use daily therapy during the intensive phase, followed by daily or three times weekly therapy during the continuation phase 1. Avoid twice-weekly dosing due to unacceptable failure and relapse rates 1.
Pregnant Women
Initiate treatment immediately when suspicion is moderate to high 1. Use the standard four-drug regimen, but streptomycin is absolutely contraindicated in pregnancy due to fetal ototoxicity 1, 4. Prophylactic pyridoxine 10 mg/day should be added 4.
Children
Use the same regimen as adults with weight-based dosing 2, 1:
- Isoniazid: 10-15 mg/kg daily (maximum 300 mg) 3
- Rifampin: 10-20 mg/kg daily (maximum 600 mg) 3
- Pyrazinamide: 15-30 mg/kg daily 3
- Ethambutol: 15-25 mg/kg daily 3
Infants and children younger than 4 years should begin treatment immediately when TB is suspected due to high risk of disseminated disease 1.
Treatment Monitoring
Obtain sputum smears and cultures at baseline, after 2 months, and at treatment completion 1. Drug susceptibility testing must be performed on all initial isolates 1. Positive sputum smears at 3 months indicate possible nonadherence or drug-resistant disease 1.
Common Pitfalls to Avoid
- Never add a single drug to a failing regimen, as this leads to further drug resistance 5
- Do not use fewer than four drugs in the initial phase, even in areas with low isoniazid resistance 5
- Avoid discontinuing ethambutol before drug susceptibility results are available 5
- Never exceed 3 grams per day of pyrazinamide when using daily dosing 6
- Do not use highly intermittent regimens (once or twice weekly) in HIV patients with CD4+ <100 cells/mm³ 5
Directly Observed Therapy
DOT is the standard of care and should be implemented for all TB patients to ensure adherence, prevent treatment failure, and avoid drug resistance 5, 7. The responsibility for ensuring treatment completion lies with the healthcare provider or public health program, not the patient 7.