What is the treatment regimen for tuberculosis (TB)?

Treatment of Tuberculosis

For drug-susceptible 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

Initial Intensive Phase (2 Months)

Use four drugs: isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) for the first 2 months. 1, 2

Dosing for Adults:

• Isoniazid: 5 mg/kg (maximum 300 mg daily) 1, 2, 3
• Rifampin: 10 mg/kg (maximum 600 mg daily) 1, 2, 4
• Pyrazinamide: 35 mg/kg daily for patients <50 kg or 2.0 g daily for patients >50 kg 2
• Ethambutol: 15 mg/kg daily 1, 2

When to Omit Ethambutol:

Ethambutol can be discontinued once drug susceptibility testing confirms the organism is susceptible to both isoniazid and rifampin. 1, 2 However, include ethambutol initially unless primary isoniazid resistance in your community is documented to be less than 4% AND the patient has no previous TB treatment, is not from a high-prevalence drug-resistance country, and has no known exposure to drug-resistant TB. 1, 5

Critical Caveat:

Always obtain drug susceptibility testing on all initial isolates before modifying the regimen. 1, 2, 4 The four-drug initial phase protects against unrecognized isoniazid resistance, which would otherwise lead to treatment failure. 1, 5

Continuation Phase (4 Months)

Use two drugs: isoniazid and rifampin for 4 months after completing the intensive phase. 1, 2

When to Extend to 7 Months:

Extend the continuation phase to 7 months (total 9 months of treatment) in these specific situations: 1

• Patients with cavitary pulmonary TB on initial chest X-ray AND positive sputum culture at completion of 2 months of treatment 1
• Patients whose initial phase did not include pyrazinamide 1
• Patients receiving once-weekly isoniazid-rifapentine who had positive culture at 2 months 1

Administration Schedule

Daily dosing is strongly recommended for both intensive and continuation phases. 1

Directly Observed Therapy (DOT):

Use DOT rather than self-administered therapy for all TB patients. 1, 2 DOT ensures treatment completion, prevents drug resistance, and allows for intermittent dosing schedules (twice or three times weekly) when daily administration is not feasible. 1 When using DOT, drugs may be given 5 days per week with doses adjusted accordingly, though this has not been compared to 7-day administration in trials. 1

Intermittent Dosing:

If daily therapy cannot be achieved, twice-weekly or three-times-weekly dosing by DOT is acceptable after an initial daily phase. 1 However, do NOT use twice-weekly dosing in HIV-infected patients with CD4 counts <100 cells/μL due to unacceptable failure rates. 1

Special Populations

HIV-Infected Patients:

Use the same 6-month regimen (2HRZE/4HR) but administer daily or three times weekly—never twice weekly if CD4 <100 cells/μL. 1 Monitor clinical and bacteriologic response closely; if response is slow or suboptimal, prolong therapy on a case-by-case basis. 5 Once-weekly isoniazid-rifapentine in the continuation phase is contraindicated in HIV-infected patients due to high failure/relapse rates with rifamycin resistance. 1

Pregnant Women:

Use isoniazid, rifampin, and ethambutol for the initial phase; avoid pyrazinamide due to inadequate teratogenicity data. 3 Never use streptomycin in pregnancy as it causes congenital deafness. 1, 3 Continue treatment for 9 months total when pyrazinamide is not used. 1

Children:

Manage children the same as adults with appropriately adjusted doses: 1, 5

• Isoniazid: 10-15 mg/kg (maximum 300 mg daily) 3
• Rifampin: 10-20 mg/kg 1
• Pyrazinamide: 15-30 mg/kg 1
• Ethambutol: 15-25 mg/kg (avoid in children too young to monitor visual acuity; use streptomycin instead) 5

Extend treatment to 12 months for miliary TB, bone/joint TB, or tuberculous meningitis in children. 5

Extrapulmonary Tuberculosis

Use the same 6-month regimen (2HRZE/4HR) for most extrapulmonary TB. 1, 2

Site-Specific Extensions:

• TB meningitis: Treat for 12 months 6
• Spinal TB with neurological involvement: Treat for 9 months 6
• Bone/joint TB in children: Treat for 12 months 5

Add adjunctive corticosteroids (dexamethasone or prednisone) for the first 6-8 weeks in: 1

• TB meningitis (to reduce neurologic sequelae) 1
• TB pericarditis (to prevent constrictive pericarditis) 1
• Spinal TB with cord compression 1

Pyridoxine Supplementation

Add pyridoxine (vitamin B6) 25-50 mg daily to all patients receiving isoniazid who are at risk for neuropathy: 1, 2

• Pregnant women 1, 2
• Breastfeeding infants 1, 2
• HIV-infected patients 1, 2
• Patients with diabetes, alcoholism, malnutrition, or chronic renal failure 1, 2
• Elderly patients 1

Increase to 100 mg daily if peripheral neuropathy develops. 1

Monitoring Treatment Response

Monitor response with follow-up sputum smear microscopy and culture at completion of the intensive phase (2 months) and at treatment completion. 1 If cultures remain positive at 2 months in patients with cavitary disease, extend the continuation phase to 7 months. 1

Perform baseline hepatic function tests (AST/ALT and bilirubin) in: 1

• HIV-infected patients 1
• Pregnant women and those within 3 months postpartum 1
• Patients with history of chronic liver disease 1
• Regular alcohol users 1

Evaluate patients monthly for adverse effects, questioning about hepatitis symptoms and checking for clinical signs. 1 Instruct patients to stop treatment immediately and seek evaluation if symptoms of hepatitis develop. 1

Multidrug-Resistant TB (MDR-TB)

If resistance to both isoniazid and rifampin is confirmed, treatment must include at least 5-6 drugs selected based on susceptibility testing. 7 Refer immediately to a TB expert for individualized regimen design. 1, 5 MDR-TB requires prolonged treatment (typically 18-24 months) and should be managed in specialized centers. 1