What is the first line treatment for extra-pulmonary tuberculosis (XTR tb)?

First-Line Treatment for Extrapulmonary Tuberculosis

For extrapulmonary tuberculosis (excluding meningitis), the first-line treatment is a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months—the same regimen used for pulmonary tuberculosis. 1

Standard Treatment Regimen

The basic principles underlying pulmonary tuberculosis treatment apply equally to extrapulmonary disease. 1 The evidence demonstrates that 6- to 9-month regimens containing isoniazid and rifampin are highly effective for extrapulmonary tuberculosis. 1

Initial Intensive Phase (2 months)

• Isoniazid 5 mg/kg/day (up to 300 mg daily) 2
• Rifampin 10 mg/kg/day (450 mg if <50 kg; 600 mg if >50 kg) 3, 4
• Pyrazinamide 35 mg/kg/day (1.5 g if <50 kg; 2.0 g if >50 kg) 3
• Ethambutol 15 mg/kg/day 3

The four-drug regimen should be used initially until drug susceptibility is confirmed, unless isoniazid resistance is highly unlikely (community resistance <4%). 1, 5

Continuation Phase (4 months)

• Isoniazid 5 mg/kg/day (up to 300 mg daily) 2
• Rifampin 10 mg/kg/day 3, 4

Critical Exceptions Requiring Longer Treatment

Tuberculous meningitis requires 9-12 months of therapy, not 6 months. 1 This is the single most important exception to the standard 6-month regimen for extrapulmonary tuberculosis. 1

In children, disseminated tuberculosis, bone/joint tuberculosis, and tuberculous meningitis should receive 9-12 months of treatment due to inadequate data supporting shorter courses. 1

Site-Specific Considerations

The duration and approach vary minimally by anatomic site:

• Lymph node tuberculosis: 6-month standard regimen 1
• Bone and joint tuberculosis: 6-9 months (some experts favor 9 months due to difficulty assessing response) 1
• Genitourinary tuberculosis: 6 months 1
• Peritoneal tuberculosis: 6 months 1
• Pericardial tuberculosis: 6 months plus corticosteroids 1
• Meningitis: 9-12 months plus corticosteroids 1

Adjunctive Corticosteroid Therapy

Corticosteroids are strongly recommended for tuberculous pericarditis and tuberculous meningitis to prevent cardiac constriction and decrease neurologic sequelae. 1 Corticosteroids should be administered early in the disease course for maximum benefit. 1

Treatment Administration

Directly observed therapy (DOT) should always be used when treating tuberculosis, including extrapulmonary disease. 1 While daily therapy is preferred, thrice-weekly regimens can be used from the beginning with equal efficacy, provided they are directly observed. 1

Special Populations

Children

Children should receive the same regimen as adults with appropriate dose adjustments. 1, 3 Ethambutol can be safely used at 15-20 mg/kg/day even in children too young for routine eye testing when isoniazid resistance is suspected. 1

Pregnancy

All first-line drugs (isoniazid, rifampin, pyrazinamide, ethambutol) can be used during pregnancy. 6 Streptomycin should be avoided due to fetal ototoxicity. 6 Prophylactic pyridoxine 10 mg/day is recommended. 6

HIV Co-infection

The same 6-month regimen is used, but careful monitoring of clinical and bacteriologic response is critical. 7 If response is slow or suboptimal, therapy should be prolonged on a case-by-case basis. 7 Rifampin interactions with protease inhibitors and NNRTIs require careful management. 6

Monitoring Treatment Response

Bacteriologic evaluation of extrapulmonary tuberculosis is often limited by the relative inaccessibility of disease sites. 1 Response must frequently be judged based on clinical and radiographic findings rather than culture results. 1

Therapy should be prolonged for patients with tuberculosis at any site that is slow to respond. 1

Common Pitfalls to Avoid

• Never use a 6-month regimen for tuberculous meningitis—this requires 9-12 months 1
• Never add a single drug to a failing regimen—always add at least two new effective drugs to prevent further resistance 5
• Do not omit ethambutol from the initial regimen unless drug resistance is highly unlikely 1, 5
• Do not assume extrapulmonary tuberculosis requires different drugs—the same first-line agents are used 1
• Avoid intermittent therapy without direct observation—all intermittent regimens require DOT 1