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
Initial Intensive Phase (First 2 Months)
Four-drug therapy is mandatory:
- 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
- Ethambutol: 15 mg/kg daily 1, 4
Ethambutol can only be omitted if:
- Drug susceptibility testing confirms full sensitivity to isoniazid and rifampin 1
- The patient has low risk for drug resistance (community isoniazid resistance <4%, no prior TB treatment, no exposure to drug-resistant cases) 1, 5
Daily dosing is strongly recommended over intermittent therapy for optimal efficacy. 1, 4
Continuation Phase (Next 4 Months)
Two-drug therapy:
- 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, 4
Critical Treatment Modifications
Extended Duration Scenarios
9 months total treatment required for:
- Cavitary pulmonary TB with positive cultures after 2 months of treatment (2HRZE followed by 7HR) 1
- Regimens without pyrazinamide 1, 5
12 months total treatment required for:
- TB meningitis and CNS tuberculosis (2HRZE followed by 10HR) 1
- Bone/joint tuberculosis in infants and children 4
HIV Co-infection
- Use the same 6-month regimen (2HRZE/4HR) 4, 6
- Add pyridoxine 25-50 mg daily to all HIV-infected patients receiving isoniazid to prevent neurological side effects 1, 4
- Substitute rifabutin for rifampin in patients receiving protease inhibitors or NNRTIs, with appropriate dose adjustments 1, 4
- Monitor for malabsorption and consider drug level monitoring in advanced HIV disease 7
Essential Treatment Principles
Directly Observed Therapy (DOT)
- DOT is the standard of care for all TB patients to ensure adherence and prevent drug resistance 1, 4, 8
- Fixed-dose combinations of 2,3, or 4 drugs may improve adherence and prevent selective medication taking 1, 4
Drug Susceptibility Testing
- Perform drug susceptibility testing on all initial isolates 6, 3
- Alter the regimen appropriately once results are available 6
Monitoring Response
- Monitor pulmonary TB with follow-up sputum smear microscopy and culture 1
- Consider rifampin blood level monitoring if poor response suggests under-dosing or malabsorption 1, 4
Critical Pitfalls to Avoid
Hepatotoxicity monitoring:
- Monitor patients for hepatotoxicity, especially during the first 2 months of treatment 1
- In patients with pre-existing liver disease but normal liver enzymes, all drugs may be used with frequent monitoring 7
Drug interactions:
- Rifampin interacts with oral contraceptives, anticoagulants, and antiretroviral drugs, requiring careful medication review and potential dose adjustments 1
- Rifampin increases clearance of cyclosporin in post-transplant patients 7
Never discontinue ethambutol before drug susceptibility results are available unless the patient meets all low-risk criteria. 1, 6
Avoid intermittent dosing (twice or thrice weekly) unless directly observed therapy is guaranteed, particularly for disseminated or severe disease. 6
Multidrug-Resistant TB
For rifampin-resistant or multidrug-resistant TB (resistance to at least isoniazid and rifampin), specialized regimens based on drug susceptibility testing are required, and consultation with TB experts is strongly recommended. 1, 4