What is the standard treatment regimen for tuberculosis?

Standard Treatment Regimen for Tuberculosis

The standard treatment for drug-susceptible tuberculosis is a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) for 2 months, followed by isoniazid and rifampin (HR) for 4 months, with daily dosing strongly recommended. 1, 2, 3, 4

Initial Intensive Phase (First 2 Months)

The intensive phase uses four drugs administered daily:

• Isoniazid: 5 mg/kg up to 300 mg daily 1, 4
• Rifampin: 10 mg/kg daily (450 mg for adults <50 kg; 600 mg for adults ≥50 kg) 1, 2
• Pyrazinamide: 35 mg/kg daily (1.5 g for adults <50 kg; 2.0 g for adults ≥50 kg) 1, 3
• Ethambutol: 15 mg/kg daily 1, 2

Ethambutol may be omitted only if drug susceptibility testing confirms full sensitivity to isoniazid and rifampin AND the community prevalence of isoniazid resistance is ≤4%. 2, 4 However, in most clinical settings where resistance patterns are uncertain, all four drugs should be used initially. 1

Continuation Phase (Next 4 Months)

• After completing 2 months of HRZE, continue with isoniazid and rifampin only for an additional 4 months 1, 2, 3
• The continuation phase can begin once susceptibility to isoniazid and rifampin is confirmed 1, 2
• Daily dosing remains strongly recommended over intermittent dosing for optimal efficacy 1, 2

Critical Duration Extensions

Certain clinical scenarios require longer treatment:

• Cavitary pulmonary TB with positive cultures at 2 months: Extend continuation phase to 7 months (total 9 months) 2
• TB meningitis and CNS tuberculosis: 12 months total (2 months HRZE + 10 months HR) 2
• Bone and joint tuberculosis: Some experts recommend 9-12 months due to limited data in extrapulmonary disease 1
• Regimens without pyrazinamide: Extend to 9 months total 2

Treatment Adherence and Monitoring

• Directly observed therapy (DOT) is the standard of care, with a treatment supporter acceptable to both patient and health system identified 1, 4
• Fixed-dose combinations of 2,3, or 4 drugs may improve adherence and prevent selective medication taking 1, 2
• Monitor response with follow-up sputum smear microscopy and culture in pulmonary TB 2
• Rifampin blood levels may be monitored if poor response suggests under-dosing or malabsorption 1, 2

Special Populations

HIV Co-infection:

• The same 6-month regimen is effective, though some patients may require longer treatment 1
• Pyridoxine 25-50 mg daily must be given to all HIV-infected patients receiving isoniazid to prevent neurological side effects 1, 2
• For patients on protease inhibitors or NNRTIs, substitute rifabutin for rifampin with appropriate dose adjustments due to drug interactions 1, 2

Pregnancy:

• All standard drugs (isoniazid, rifampin, pyrazinamide, ethambutol) can be used during pregnancy 5
• Streptomycin should be avoided due to fetal ototoxicity 5
• Prophylactic pyridoxine 10 mg/day is recommended 5

Diabetes Mellitus:

• Same drug regimen as non-diabetic patients 5
• Doses of oral hypoglycemic agents may need to be increased due to rifampin interaction 5

Drug Resistance Considerations

• Treatment must be guided by genotypic and/or phenotypic drug susceptibility testing if resistance is suspected or confirmed 1
• For multidrug-resistant TB (MDR-TB): Use at least five effective drugs including a later-generation fluoroquinolone and bedaquiline unless contraindicated 1
• Rifampin mono-resistance and MDR-TB cases should be treated in specialized centers with experience in managing drug-resistant disease 1

Common Pitfalls to Avoid

• Never discontinue the intensive phase prematurely before 2 months, even if clinical improvement occurs 1
• Rifampin interacts with many medications including oral contraceptives, anticoagulants, and antiretroviral drugs, requiring careful medication review 2
• Monitor for hepatotoxicity, especially during the first 2 months of treatment 2
• Ethambutol should not be used in children whose visual acuity cannot be monitored 4