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), administered daily. 1

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, 2

• 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

• Ethambutol: 15 mg/kg daily 1

• Daily dosing is strongly recommended over intermittent regimens for optimal efficacy 1

• Ethambutol may only be omitted if drug susceptibility testing confirms full sensitivity to isoniazid and rifampin AND the patient has low risk for drug resistance (local isoniazid resistance <4%) 1, 2

• All initial isolates must undergo drug susceptibility testing 3

Continuation Phase (Next 4 Months)

After completing the intensive phase, continue with two drugs:

• 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

• Daily dosing remains the preferred approach 1

Critical 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 and CNS tuberculosis: 12 months total (2 months HRZE followed by 10 months HR) 1, 3
• Bone/joint tuberculosis in infants and children: 12 months due to inadequate evidence for shorter regimens 4
• Regimens without pyrazinamide: Extend to 9 months total 1

Treatment Adherence and Monitoring

• Directly observed therapy (DOT) is the standard of care to ensure treatment completion and prevent drug resistance 3, 2
• 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
• Clinical and radiographic monitoring is necessary for extrapulmonary TB where bacteriologic evaluation is limited 4

Essential Adjunctive Therapy

Pyridoxine (vitamin B6) supplementation:

• Give 25-50 mg daily to all HIV-infected patients receiving isoniazid to prevent neurological side effects 1
• Consider for patients with diabetes, malnutrition, or alcohol use disorder 1

Special Population Considerations

HIV Co-infection

• Use the same 6-month regimen (2HRZE/4HR) for HIV-infected patients 3, 5
• Critical drug interaction: For patients on protease inhibitors or NNRTIs, substitute rifabutin for rifampin with appropriate dose adjustments 1, 4
• Pyridoxine 25-50 mg daily is mandatory for all HIV-infected patients on isoniazid 1, 4
• Monitor for malabsorption; drug level monitoring may be necessary in advanced HIV disease 5

Pregnancy

• All first-line drugs (rifampin, isoniazid, ethambutol, pyrazinamide) can be used during pregnancy 5
• Avoid streptomycin due to fetal ototoxicity 5
• Prophylactic pyridoxine 10 mg/day is recommended 5

Renal Impairment

• Adjust doses of streptomycin, ethambutol, and isoniazid according to creatinine clearance 5
• Standard rifampin dosing can be maintained 5

Hepatic Disease

• In stable disease with normal liver enzymes, all drugs may be used with frequent liver function monitoring 5
• Rifampin-containing regimens should be avoided in post-transplant patients on cyclosporin due to increased cyclosporin clearance 5

Critical Pitfalls to Avoid

• Never use fewer than four drugs in the initial phase for disseminated TB or when drug resistance risk is present, even if local isoniazid resistance is <4% 3
• Do not discontinue ethambutol prematurely before drug susceptibility results are available 3
• Rifampin has extensive drug interactions with oral contraceptives, anticoagulants, and antiretroviral drugs—review all medications and adjust doses accordingly 1
• Monitor for hepatotoxicity closely during the first 2 months of treatment 1
• Avoid premature discontinuation of the intensive phase before 2 months, even with clinical improvement 4
• Do not use intermittent dosing for disseminated or severe TB unless DOT is guaranteed 3

Drug-Resistant Tuberculosis

• For rifampin-resistant or multidrug-resistant TB, specialized regimens based on drug susceptibility testing are required 1
• Consultation with TB experts is mandatory for MDR-TB cases 1, 4
• MDR-TB requires at least five effective drugs including a later-generation fluoroquinolone and bedaquiline unless contraindicated 4