What is the recommended treatment regimen for multidrug-resistant (MDR) tuberculosis?

Treatment for Multidrug-Resistant Tuberculosis (MDR-TB)

The recommended treatment regimen for MDR-TB should include all three Group A drugs (bedaquiline, linezolid, and a fluoroquinolone) plus at least one Group B agent to ensure treatment starts with at least four effective TB agents. 1, 2

Drug Selection Algorithm

Group A Drugs (Include All):

1. Bedaquiline

   • Strongly recommended for patients ≥18 years 1
   • Conditionally recommended for ages 6-17 years 1
   • Monitoring: ECG after initial 2 weeks then monthly for QT prolongation 2

2. Linezolid

   • Strongly recommended for all MDR-TB patients 1
   • Monitor for myelosuppression and peripheral neuropathy

3. Fluoroquinolone

   • Levofloxacin or moxifloxacin (strongly recommended) 1
   • Moxifloxacin may be more effective for culture conversion 3

Group B Drugs (Include At Least One):

1. Clofazimine (conditional recommendation) 1
2. Cycloserine/Terizidone (conditional recommendation) 1

Additional Drugs (As Needed):

1. Delamanid - may be included for patients ≥3 years 1
2. Ethambutol - only when more effective drugs cannot be assembled 1
3. Pyrazinamide - when susceptibility is confirmed or likely 1

Important Considerations

Drugs to Avoid:

• Do NOT include kanamycin or capreomycin 1
• Do NOT include amoxicillin-clavulanate except when using with a carbapenem 1
• Do NOT include macrolides (azithromycin, clarithromycin) 1
• Avoid ethionamide/prothionamide if more effective drugs are available 1
• Avoid p-aminosalicylic acid if more effective drugs are available 1

Injectable Agents:

• Only include amikacin or streptomycin when susceptibility is confirmed 1
• Consider a carbapenem (with amoxicillin-clavulanate) if needed 1

Treatment Duration and Monitoring

• Total treatment duration: 18-20 months for most patients 2
• Post-culture conversion duration: 15-17 months after culture conversion 2
• Regular monitoring:
  • Monthly sputum cultures to assess treatment response
  • ECG monitoring for QT prolongation (especially with bedaquiline)
  • Electrolyte monitoring (calcium, magnesium, potassium) 2
  • Monitor for drug-specific adverse effects

Special Considerations

• Regimens with at least six potentially effective drugs may increase likelihood of sputum culture conversion by 36% compared to regimens with 5 drugs 4
• Drug susceptibility testing (DST) results should guide therapy whenever possible 4
• Including drugs with confirmed susceptibility has greater benefit than including drugs with unknown susceptibility 4
• Bedaquiline's unique mechanism of action (ATP synthase inhibition) makes it effective against both replicating and dormant mycobacteria 5
• For patients failing standard MDR-TB regimens, salvage therapy with new drugs may be necessary 3

Pitfalls to Avoid

1. Inadequate number of effective drugs: Always ensure at least 4-5 effective drugs are included
2. Ignoring drug susceptibility testing: DST results significantly improve treatment outcomes
3. Inappropriate injectable use: Avoid kanamycin and capreomycin due to poor efficacy and toxicity
4. Inadequate monitoring: Regular clinical, bacteriological, and adverse effect monitoring is essential
5. Premature discontinuation: Complete the full treatment course to prevent relapse and resistance

By following this evidence-based approach to MDR-TB treatment, focusing on the most effective drugs while monitoring for adverse effects, patients have the best chance for successful treatment outcomes and improved survival.