What is the treatment for disseminated tuberculosis?

Treatment of Disseminated Tuberculosis

For disseminated tuberculosis, treatment should consist of a 6-month regimen with rifampicin, isoniazid, and pyrazinamide for the first 2 months, followed by rifampicin and isoniazid for 4 months, with the addition of ethambutol in the initial phase unless there is low risk of isoniazid resistance. 1

Standard Treatment Regimen

Initial Phase (First 2 Months):

• Rifampicin
• Isoniazid
• Pyrazinamide
• Ethambutol (can be omitted in previously untreated patients with low risk of drug resistance)

Continuation Phase (Next 4 Months):

• Rifampicin
• Isoniazid

Special Considerations

Extended Treatment Duration

• If central nervous system involvement is present, treatment should be extended to 9-12 months 1, 2
• If pyrazinamide cannot be tolerated, treatment should be extended to 9 months with ethambutol given for the initial 2 months 1

Pediatric Patients

• Children with disseminated tuberculosis should receive the same 6-month regimen as adults 1
• For children with CNS involvement, treatment should be extended to 9-12 months 1
• Ethambutol is not used routinely in young children due to difficulty monitoring visual acuity 1

Monitoring Requirements

• Regular clinical assessment for treatment response
• Monitoring for drug toxicity:
  • Liver function tests (especially with rifampicin, isoniazid, and pyrazinamide) 3
  • Visual acuity and color discrimination if using ethambutol 2
  • Renal function if using streptomycin 2

Drug Toxicity Considerations

Common Adverse Effects

• Isoniazid: Hepatitis and peripheral neuropathy (preventable with pyridoxine) 3
• Rifampicin: Generally well tolerated but can cause immunoallergic reactions 3
• Pyrazinamide: Joint pain due to hyperuricemia, rare but potentially severe hepatotoxicity 3
• Ethambutol: Optic neuropathy (dose-dependent, potentially irreversible) 3
• Streptomycin: Renal and cochleo-vestibular toxicity 3

Special Populations

HIV Co-infection

• Same principles apply as for non-HIV patients with two exceptions 1:
  1. Once-weekly isoniazid-rifapentine should not be used
  2. Twice-weekly isoniazid-rifampin/rifabutin should not be used in patients with CD4+ counts <100/mm³
• More careful monitoring of treatment response is required
• Drug interactions between rifamycins and antiretrovirals must be managed

Renal Disease

• Rifampicin, isoniazid, and pyrazinamide can be given in standard doses 1
• If streptomycin or ethambutol are used, doses should be reduced and serum concentrations monitored 1
• For patients on dialysis, medications should be administered after dialysis 1

Liver Disease

• Despite hepatotoxicity risks, first-line drugs should still be used if possible due to their effectiveness 1
• More frequent monitoring of liver function is required:
  • Weekly for first two weeks
  • Every two weeks thereafter during initial phase 1

Pregnancy

• Standard treatment can be given during pregnancy 1
• Streptomycin should be avoided due to risk of fetal ototoxicity 1
• Women should be advised about reduced effectiveness of oral contraceptives when taking rifampicin 1

Treatment Adherence and Completion

• Treatment completion is determined by the number of doses taken, not just duration 1
• All doses for the initial phase should be delivered within 3 months
• All doses for the continuation phase should be delivered within 6 months
• The full 6-month regimen should be completed within 9 months 1

Pitfalls to Avoid

1. Failing to extend treatment duration when CNS involvement is present
2. Omitting ethambutol when there is significant risk of drug resistance
3. Inadequate monitoring for drug toxicity, especially hepatotoxicity
4. Not recognizing drug interactions, particularly with rifampicin
5. Premature discontinuation of therapy before completing the full course

Remember that disseminated tuberculosis represents a serious form of the disease with potential involvement of multiple organ systems, requiring careful monitoring and management of complications throughout the treatment course.