Treatment of Extrapulmonary Tuberculosis
For drug-susceptible extrapulmonary TB, treat with the standard 6-month regimen of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months—the same regimen used for pulmonary TB. 1, 2, 3
Standard Drug-Susceptible Regimen
Initial Phase (2 months)
- Four drugs daily: Isoniazid, rifampin, pyrazinamide, and ethambutol 1, 4
- Ethambutol can be omitted if drug susceptibility testing confirms no isoniazid resistance and community resistance rates are <4% 1, 4
- Dosing: Rifampin 10 mg/kg (max 600 mg/day), administered 1 hour before or 2 hours after meals 2
Continuation Phase (4 months)
- Two drugs: Isoniazid and rifampin daily or twice weekly under directly observed therapy (DOT) 1, 4
- For severe extrapulmonary disease (miliary TB, bone/joint TB, or TB meningitis in children), extend total duration to 12 months minimum 4, 5
Critical Site-Specific Considerations
When to Extend Beyond 6 Months
- TB meningitis, miliary TB, or bone/joint involvement: Treat for 9-12 months 6, 4
- Spinal TB with neurologic complications: Consider 12-18 months based on clinical response 6
- The American College of Physicians recommends 9-18 months for TB osteoarticular disease depending on severity and response 6
HIV-Positive Patients
- Use the same initial regimen but extend treatment to minimum 9 months and at least 6 months beyond documented culture conversion (three negative cultures) 1, 4
- Assess clinical and bacteriologic response carefully; if slow or suboptimal, prolong therapy on a case-by-case basis 4
Drug-Resistant Extrapulmonary TB
Isoniazid-Resistant, Rifampin-Susceptible Disease
- 6-month regimen: Rifampin, ethambutol, pyrazinamide, plus a later-generation fluoroquinolone (levofloxacin preferred over moxifloxacin) 6, 7
- Do NOT add injectable agents like streptomycin 7
MDR/RR-TB (Multidrug-Resistant/Rifampin-Resistant)
- First-line approach: BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin) for 6 months if no documented fluoroquinolone or bedaquiline resistance 8, 7
- This applies to extrapulmonary disease including intestinal TB 8
- If fluoroquinolone resistance exists, use individualized longer regimen (18-20 months) with at least 5 effective drugs 1, 7
Longer MDR-TB Regimens
- Core drugs: Levofloxacin or moxifloxacin, bedaquiline, and linezolid 7
- Additional agents: At least one of clofazimine or cycloserine, plus supplementary drugs (ethambutol, delamanid, pyrazinamide) 7
- Avoid: Kanamycin and capreomycin due to toxicity without proven benefit 6, 7
Essential Management Principles
Directly Observed Therapy
- Strongly recommended for all TB patients to ensure adherence and prevent resistance 7
- Intermittent dosing (twice or three times weekly) acceptable during continuation phase under DOT 1
Monitoring Requirements
- Monthly sputum cultures until negative (for pulmonary involvement) 1, 8
- Expect sputum conversion within 3 months; if not achieved, evaluate for non-adherence and drug resistance 1
- Monitor for hepatotoxicity: Instruct patients to report loss of appetite, nausea, vomiting, jaundice, or unexplained fever >3 days 1
Critical Pitfalls to Avoid
- Never add a single drug to a failing regimen—this rapidly leads to acquired resistance 6
- Consult a TB expert for all suspected or confirmed drug-resistant cases 1
- For patients on methadone, increase methadone dose when starting rifampin to avoid withdrawal 1
- Give pyridoxine 50 mg daily with isoniazid in patients with diabetes, uremia, alcoholism, malnutrition, or pregnancy 1
Adjunctive Surgery
- Consider for bone/joint TB when no response after 4-5 months of appropriate chemotherapy, severe cartilage destruction, large abscesses, pathologic fracture, or spinal cord compression 6
- For MDR/XDR-TB with lung involvement, lung resection surgery may improve outcomes in select cases receiving antimicrobial therapy 1