What is the recommended treatment regimen for Multi-Drug Resistant (MDR) Tuberculosis (TB)?

Treatment Regimen for Multi-Drug Resistant Tuberculosis (MDR-TB)

The recommended treatment for MDR-TB should include a combination of bedaquiline, linezolid, and a fluoroquinolone (levofloxacin or moxifloxacin), plus at least one additional effective drug to ensure treatment starts with at least four effective TB agents, with a total duration of 15-24 months after culture conversion. 1, 2

Core Drug Selection

Group A Drugs (Include All):

• Bedaquiline: Strongly recommended for patients ≥18 years (strong recommendation) and conditionally for ages 6-17 years 1, 2
• Linezolid: Strongly recommended for all MDR-TB patients 1, 2
• Fluoroquinolone: Either levofloxacin or moxifloxacin (strong recommendation) 1, 2

Group B Drugs (Add at least one):

• Clofazimine: Suggested for inclusion in regimens 1, 2
• Cycloserine: Suggested for inclusion in regimens 1, 2

Additional Drugs to Consider:

• Ethambutol: Only when other more effective drugs cannot be assembled to achieve five drugs in the regimen 1
• Pyrazinamide: Consider including when the isolate has not been found resistant to it 1
• Delamanid: May be included for patients aged ≥3 years on longer regimens 1, 2

Drugs to Avoid

• Kanamycin and capreomycin: Not recommended for inclusion in MDR-TB regimens 1
• Amoxicillin-clavulanate: Not recommended except when using a carbapenem 1
• Macrolides (azithromycin, clarithromycin): Not recommended 1
• Ethionamide/prothionamide: Not recommended if more effective drugs are available 1, 3
• p-aminosalicylic acid: Not recommended if more effective drugs are available 1

Treatment Duration

• Total treatment duration: 18-20 months for most patients 2
• Post-culture conversion duration: 15-24 months after culture conversion 1, 2

Drug Susceptibility Testing (DST)

• DST is crucial for optimizing the regimen composition 1
• At minimum, testing for fluoroquinolones, bedaquiline, and linezolid susceptibility should be performed before treatment initiation 4
• Countries with insufficient laboratory capacity for DST should prioritize strengthening this capacity 1

Monitoring and Safety

• ECG monitoring: After initial 2 weeks of bedaquiline therapy and then monthly to monitor QT interval prolongation, especially when combining bedaquiline, moxifloxacin, and clofazimine 2, 4
• Electrolyte monitoring: Regular monitoring of serum calcium, magnesium, and potassium 2
• Adverse effects: Close monitoring for linezolid toxicity (peripheral neuropathy, myelosuppression) and cycloserine adverse effects (neuropsychiatric) 2, 4

Special Considerations

• For patients with fluoroquinolone resistance, linezolid becomes particularly important, as it significantly improves outcomes in FQ-resistant MDR/XDR-TB (82.8% favorable outcomes with linezolid vs. 58.1% without) 5
• Directly observed therapy is strongly recommended to ensure adherence and prevent further resistance development 1, 3

Treatment Approach Algorithm

1. Confirm MDR-TB diagnosis and obtain drug susceptibility testing
2. Start with all three Group A drugs (bedaquiline, linezolid, fluoroquinolone)
3. Add at least one Group B drug (clofazimine or cycloserine)
4. If needed to reach at least 4-5 effective drugs, consider additional agents
5. Monitor for treatment response and adverse effects
6. Continue treatment for 15-24 months after culture conversion

The evidence strongly supports this approach to maximize treatment success while minimizing mortality and preserving quality of life in patients with MDR-TB.