What is the recommended treatment regimen for drug-resistant tuberculosis?

Recommended Treatment Regimen for Drug-Resistant Tuberculosis

The recommended treatment regimen for drug-resistant tuberculosis should include bedaquiline, a later-generation fluoroquinolone (levofloxacin or moxifloxacin), and linezolid as core components, supplemented with clofazimine and cycloserine, for a total of at least five effective drugs in the intensive phase and four drugs in the continuation phase. 1, 2

Core Components of MDR-TB Treatment

• At least five effective drugs should be used in the intensive phase and four drugs in the continuation phase of treatment 1
• The intensive phase duration should be 5-7 months after culture conversion 1
• Total treatment duration should be 15-21 months after culture conversion for MDR-TB, and 15-24 months for pre-XDR and XDR-TB 1, 2

Essential Drugs to Include (Group A - Highest Priority)

• Bedaquiline: Strongly recommended as a core component of any MDR-TB regimen 1

  • Has shown significant improvement in treatment outcomes with 78% culture conversion rates at 6 months 3
  • Should be administered at 200 mg daily for 8 weeks, followed by 100 mg daily for the remainder of treatment 4

• Later-generation fluoroquinolone: Either levofloxacin or moxifloxacin is strongly recommended 1

  • These are considered essential components with moderate certainty of evidence 1
  • Caution should be exercised when combining moxifloxacin with bedaquiline and clofazimine due to potential QT interval prolongation 5

• Linezolid: Strongly recommended as a core component 1

  • Optimal dosing appears to be 600 mg daily for 26 weeks, which balances efficacy with lower toxicity 4
  • Monitoring for peripheral neuropathy and myelosuppression is essential 4

Additional Effective Drugs (Group B - Second Priority)

• Clofazimine: Conditionally recommended as an important component 1

  • Particularly valuable in fluoroquinolone-resistant cases 2
  • Monitor for skin discoloration and QT interval prolongation 5

• Cycloserine or terizidone: Conditionally recommended 1

  • Effective component but requires monitoring for neuropsychiatric adverse effects 2

Supplementary Drugs (Group C - Add When Needed)

• Pyrazinamide: Should only be included if susceptibility is confirmed 1

  • Not recommended if resistance is documented or suspected 1

• Ethambutol: Should only be included when more effective drugs cannot be assembled to achieve a total of five drugs 1

• Delamanid: May be included for patients aged ≥3 years 1

  • Evidence is limited but WHO provides a conditional recommendation 1

Drugs to Avoid

• Kanamycin and capreomycin: Not recommended due to poor outcomes and toxicity 1
• Macrolides (azithromycin and clarithromycin): Not recommended due to lack of efficacy 1
• Amoxicillin-clavulanate: Only recommended when used with a carbapenem 1
• Ethionamide/prothionamide: Not recommended if more effective drugs are available 1

Special Considerations for XDR-TB

• For XDR-TB (resistant to rifampicin, fluoroquinolones, and at least one additional Group A drug), consider:
  • Bedaquiline-pretomanid-linezolid regimen has shown 84-93% favorable outcomes 4
  • Extended treatment duration of 15-24 months after culture conversion 2
  • Consider surgical intervention in selected cases with localized disease 2

Monitoring and Management

• Regular monitoring for adverse effects is essential, particularly:

  • QT interval prolongation with bedaquiline, moxifloxacin, and clofazimine 5
  • Peripheral neuropathy and myelosuppression with linezolid 4
  • Neuropsychiatric effects with cycloserine 2

• Drug susceptibility testing should ideally be performed for fluoroquinolones, bedaquiline, and linezolid before treatment initiation 5

Common Pitfalls to Avoid

• Using fewer than five effective drugs in the intensive phase leads to poorer outcomes 2
• Treating for less than the recommended duration increases relapse risk 2
• Failing to monitor for and manage adverse effects can lead to treatment interruptions and compromised efficacy 5, 4
• Not confirming drug susceptibility before treatment can lead to acquired resistance, particularly to bedaquiline when undetected fluoroquinolone resistance is present 5

The evidence strongly supports an all-oral regimen centered around bedaquiline, a fluoroquinolone, and linezolid, with additional drugs to complete a regimen of at least five effective medications during the intensive phase of treatment 1, 2.