Standard Treatment Regimen for Extrapulmonary Tuberculosis (EPTB)
For most extrapulmonary tuberculosis sites, treat with the same 6-month regimen used for pulmonary TB: 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (2HRZE), followed by 4 months of isoniazid and rifampin (4HR). 1, 2, 3
Initial Intensive Phase (2 Months)
The first 2 months should include all four drugs given daily 1, 2:
- Isoniazid: 5 mg/kg up to 300 mg daily 1, 3, 4
- Rifampin: 10 mg/kg (450 mg if <50 kg; 600 mg if ≥50 kg) 3
- Pyrazinamide: 35 mg/kg (1.5 g if <50 kg; 2.0 g if ≥50 kg) 3
- Ethambutol: 15 mg/kg daily 1, 3
Daily dosing is strongly recommended over intermittent regimens for optimal efficacy 1, 3. Ethambutol can be discontinued once drug susceptibility confirms full susceptibility to isoniazid and rifampin 2.
Continuation Phase (4 Months)
After the initial 2 months, continue with isoniazid and rifampin only for an additional 4 months 1, 3. The continuation phase can begin once susceptibility to isoniazid and rifampin is confirmed 1, 3.
Critical Site-Specific Exceptions
TB Meningitis: Extended Duration Required
TB meningitis requires 12 months of treatment, not 6 months 1. Use rifampin and isoniazid for the full 12 months, with pyrazinamide for the initial 2 months, plus a fourth drug (streptomycin or ethambutol) 1. Adjunctive corticosteroids (dexamethasone or prednisone) should be given during the first 6-8 weeks 1.
Bone and Joint TB: Consider Extended Duration
While the standard 6-month regimen is recommended for bone and joint tuberculosis in adults 1, 3, the British Thoracic Society recommends 12 months of therapy for bone/joint tuberculosis in infants and children due to inadequate evidence for shorter regimens 3. Some experts recommend extending treatment to 9-12 months for bone and joint tuberculosis in all patients due to limited data in extrapulmonary disease 3.
Spinal TB with Neurological Involvement
For spinal TB with evidence of spinal cord compression, use the standard 6-month regimen but add adjunctive corticosteroids 1, 3. Some guidelines suggest extending treatment to 9 months in cases with neurological involvement 5.
Other EPTB Sites
For tuberculous adenitis, bowel disease, pericarditis, genitourinary TB, and other end organ disease, the standard 6-month regimen is recommended 1, 3. For TB pericarditis, adjunctive corticosteroids should be used to prevent constrictive pericarditis 1. For renal TB, corticosteroids may prevent ureteric stenosis 1.
Monitoring Response in EPTB
Response to treatment in EPTB must often be judged on clinical and radiographic findings rather than bacteriologic evaluation, as sites of disease are relatively inaccessible 3, 4, 6. Serial synovial fluid cultures may be difficult to obtain in joint TB 3. Monitor rifampin blood levels if poor response suggests under-dosing or malabsorption 1, 3.
Directly Observed Therapy
All patients should receive directly observed therapy (DOT) to ensure adherence 1, 3, 6. Patient-centered DOT with a treatment supporter acceptable to both patient and health system should be identified 3.
Special Populations
HIV Co-infection
The same 6-month regimen is effective in HIV-positive patients, though some may require longer treatment 3. Pyridoxine 25-50 mg daily must be given to all HIV-infected patients receiving isoniazid 2, 3. For patients on protease inhibitors or NNRTIs, substitute rifabutin for rifampin with appropriate dose adjustments 2, 3.
Pregnancy
Standard treatment should be given to pregnant women 1. All first-line drugs (isoniazid, rifampin, pyrazinamide, ethambutol) can be used during pregnancy 7. Streptomycin and other aminoglycosides should be avoided as they may be ototoxic to the fetus 1. Prophylactic pyridoxine 10 mg/day is recommended 7.
Children
Children should receive appropriately adjusted doses: isoniazid 10-15 mg/kg up to 300 mg daily, with the same four-drug regimen 1, 4. For children with bone/joint TB or miliary TB, extend treatment to 12 months 1, 3, 6.
Common Pitfalls to Avoid
- Do not prematurely discontinue the intensive phase before 2 months, even if clinical improvement occurs 3
- Do not use the 6-month regimen for TB meningitis—this requires 12 months 1
- Do not forget pyridoxine supplementation in HIV-infected patients, breast-fed infants, and malnourished children 1, 2, 3
- Monitor for hepatotoxicity, especially during the first 2 months, with weekly liver function tests for the first two weeks in patients with chronic liver disease 1
- Fixed-dose combinations of 2,3, or 4 drugs may improve adherence and prevent selective medication taking 1, 3