Treatment of Drug-Susceptible Tuberculosis
For drug-susceptible pulmonary tuberculosis, treat with a 6-month regimen consisting of 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (2HRZE), followed by 4 months of isoniazid and rifampin (4HR). 1, 2, 3
Initial Intensive Phase (First 2 Months)
Administer four drugs daily:
- Isoniazid: 5 mg/kg (maximum 300 mg) daily 2, 3
- Rifampin: 10 mg/kg (maximum 600 mg) daily; use 450 mg if <50 kg body weight 1, 2
- Pyrazinamide: 35 mg/kg daily for patients <50 kg or 2.0 g daily for patients ≥50 kg 2, 4
- Ethambutol: 15 mg/kg daily 2, 5
Ethambutol may be omitted only if: drug susceptibility testing confirms full sensitivity to isoniazid and rifampin AND the patient has documented low risk for drug resistance (community isoniazid resistance rate ≤4%) 1, 3
Continuation Phase (Next 4 Months)
Administer two drugs daily:
Extended Treatment Scenarios
Extend continuation phase to 7 months (total 9 months) if: the patient has cavitary pulmonary TB on initial chest radiograph AND sputum culture remains positive after completing 2 months of treatment 1, 2
Treat for 12 months total if: the patient has TB meningitis or CNS tuberculosis (2 months HRZE followed by 10 months HR) 1
Treat for 9 months total if: pyrazinamide cannot be included in the initial regimen (2 months HRE followed by 7 months HR) 1
Administration and Monitoring
Use directly observed therapy (DOT) for all TB patients to ensure treatment completion, prevent drug resistance, and enhance TB control 2, 3, 6
Monitor treatment response with:
- Sputum smear microscopy and culture at 2 months (completion of intensive phase) 1, 2
- Sputum smear microscopy and culture at treatment completion 2
Obtain baseline hepatic function tests (AST/ALT and bilirubin) in: HIV-infected patients, pregnant women, patients with chronic liver disease history, and regular alcohol users 2
Essential Adjunctive Therapy
Add pyridoxine (vitamin B6) 25-50 mg daily to all patients receiving isoniazid who have: pregnancy, breastfeeding, HIV infection, diabetes, alcoholism, malnutrition, or chronic renal failure 1, 2
Special Populations
HIV Co-infected Patients
Use the same 6-month regimen (2HRZE/4HR) with daily dosing throughout both phases 2
Never use once- or twice-weekly dosing if CD4 count <100 cells/mm³ due to increased risk of rifampin resistance 7, 2
If receiving protease inhibitors or NNRTIs: substitute rifabutin for rifampin with appropriate dose adjustments 1
Pregnant Women
Use isoniazid, rifampin, and ethambutol for the initial phase 3
Avoid streptomycin (causes congenital deafness) 3
Pyrazinamide is not routinely recommended due to inadequate teratogenicity data, though some guidelines now support its use 3
Children
Use 10-15 mg/kg isoniazid (maximum 300 mg) daily 3
Avoid ethambutol in young children whose visual acuity cannot be monitored 3
Isoniazid-Resistant, Rifampin-Susceptible TB
Treat with rifampin, ethambutol, pyrazinamide, and a later-generation fluoroquinolone (levofloxacin or moxifloxacin) for 6 months 7
In noncavitary disease with low bacillary burden: pyrazinamide may be shortened to 2 months only, provided a later-generation fluoroquinolone is used 7
Critical Pitfalls to Avoid
Never add a single drug to a failing regimen as this leads to resistance to the added drug 7
Never treat with a single drug as this causes mycobacterial resistance 7
Rifampin interacts with numerous medications including oral contraceptives, anticoagulants, and antiretroviral drugs—review all medications and adjust doses accordingly 1
Monitor for hepatotoxicity closely during the first 2 months when risk is highest 2
If treatment is interrupted: the earlier the interruption and the longer its duration, the more likely you need to restart treatment from the beginning, especially if interruption occurs during the initial 2-month phase when bacillary burden is highest 7