What is the standard treatment regimen for tuberculosis (TB)?

Standard Treatment Regimen for Tuberculosis

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

Initial Intensive Phase (First 2 Months)

Four-drug therapy is mandatory for the first 2 months:

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

Daily dosing is strongly preferred over intermittent regimens for optimal efficacy. 1

When Ethambutol Can Be Omitted

• Ethambutol may be discontinued once drug susceptibility testing confirms full sensitivity to isoniazid and rifampin, AND the patient has low risk for drug resistance (local isoniazid resistance <4%) 1, 3
• However, ethambutol should be included initially in all cases until susceptibility is confirmed 1

Continuation Phase (Next 4 Months)

After completing 2 months of four-drug therapy, continue with isoniazid and rifampin only:

• Isoniazid: 5 mg/kg up to 300 mg daily 1
• Rifampin: 10 mg/kg daily (450 mg for adults <50 kg; 600 mg for adults ≥50 kg) 1
• The continuation phase begins once susceptibility to isoniazid and rifampin is confirmed 1

Treatment Duration Modifications

Extend treatment beyond 6 months in these specific situations:

• Cavitary pulmonary TB with positive cultures at 2 months: Extend continuation phase to 7 months (total 9 months) 1
• TB meningitis or CNS tuberculosis: Treat for 12 months total (2 months HRZE, then 10 months HR) 1
• Regimens without pyrazinamide: Extend to 9 months total 1
• Bone/joint tuberculosis in infants and children: Treat for 12 months due to inadequate evidence for shorter regimens 4

Special Population Considerations

HIV Co-infection

• Use the same 6-month regimen (2HRZE/4HR) for HIV-infected patients 5, 6
• Add pyridoxine (vitamin B6) 25-50 mg daily to all HIV-infected patients receiving isoniazid to prevent neurological side effects 1, 5
• For patients on protease inhibitors or NNRTIs, substitute rifabutin for rifampin with appropriate dose adjustments 1, 5

Pregnancy

• All first-line drugs (isoniazid, rifampin, pyrazinamide, ethambutol) can be used safely during pregnancy 6
• Avoid streptomycin due to fetal ototoxicity 6
• Add prophylactic pyridoxine 10 mg daily 6

Diabetes Mellitus

• Use the standard regimen with strict glucose control 6
• Increase oral hypoglycemic doses due to rifampin interaction 6
• Add prophylactic pyridoxine 6

Treatment Adherence and Monitoring

Directly observed therapy (DOT) is the standard of care to ensure adherence and prevent drug resistance: 1, 3

• Fixed-dose combinations of 2,3, or 4 drugs improve adherence and prevent selective medication taking 1, 4
• Monitor response with follow-up sputum smear microscopy and culture in pulmonary TB 1
• Monitor for hepatotoxicity, especially during the first 2 months 1

Critical Drug Interactions and Monitoring

Rifampin has significant drug interactions requiring careful medication review:

• Interacts with oral contraceptives, anticoagulants, and antiretroviral drugs 1
• Induces metabolism of many medications, requiring dose adjustments 1
• Monitor rifampin blood levels if poor response suggests under-dosing or malabsorption 1, 4

Drug Resistance Considerations

For rifampin-resistant or multidrug-resistant TB:

• Specialized regimens based on drug susceptibility testing are required 1
• Consultation with TB experts is mandatory 1
• Use at least five effective drugs including a later-generation fluoroquinolone and bedaquiline unless contraindicated 4

Drug susceptibility testing should be performed on all initial isolates to guide therapy appropriately. 3, 6

Common Pitfalls to Avoid

• Never use fewer than four drugs in the initial phase, even if local isoniazid resistance is low 5
• Do not discontinue ethambutol before drug susceptibility results are available 5
• Avoid premature discontinuation of the intensive phase before 2 months, even with clinical improvement 4
• Do not use intermittent (twice or thrice weekly) dosing unless directly observed therapy is guaranteed 5