Current Management of MDR TB
For patients with multidrug-resistant tuberculosis (MDR-TB), a regimen containing all three Group A drugs (bedaquiline, linezolid, and a fluoroquinolone) plus at least one Group B agent should be used to ensure treatment starts with at least four effective TB agents. 1
Classification of Anti-TB Drugs for MDR-TB Treatment
The WHO classifies drugs for MDR-TB treatment into three priority groups:
Group A: Highly Effective Drugs (Include All Three)
- Bedaquiline: Strong recommendation for patients ≥18 years; conditional recommendation for ages 6-17 years 1
- Linezolid: Strong recommendation 1
- Fluoroquinolone: Either levofloxacin or moxifloxacin (strong recommendation) 1
Group B: Conditionally Recommended Drugs (Add At Least One)
Group C: Add When Group A and B Cannot Complete the Regimen
- Delamanid: For patients ≥3 years 1
- Ethambutol 1
- Pyrazinamide 1
- Imipenem-cilastatin or meropenem (with clavulanic acid) 1
- Amikacin (or streptomycin): Only when susceptibility is confirmed and monitoring for adverse reactions is possible 1
- Ethionamide/prothionamide: Only if Group A and better Group B/C drugs cannot be used 1
- p-Aminosalicylic acid: Only if Group A and better Group B/C drugs cannot be used 1
Drugs to Avoid
- Kanamycin and capreomycin: Should not be included in MDR-TB regimens 1
- Amoxicillin-clavulanate: Should not be used except to provide clavulanate when using a carbapenem 1
Treatment Duration and Administration
- Total treatment duration: 18-20 months for most patients 1
- Post-culture conversion duration: 15-17 months after culture conversion 1
- Bedaquiline dosing: 400 mg once daily for 2 weeks, followed by 200 mg three times weekly for 22 weeks 1, 2
Special Considerations
Monitoring
- ECG monitoring: Most experts obtain ECGs after the initial 2 weeks of bedaquiline therapy and then monthly to monitor for QT interval prolongation 1
- Electrolyte monitoring: Serum calcium, magnesium, and potassium should be monitored 1
Drug Interactions
- Bedaquiline metabolism: Metabolized by CYP3A4; interactions with inducers and inhibitors should be monitored 2
- Food effect: Bedaquiline should be administered with food, which increases bioavailability 2-fold 2
Treatment Interruptions
- For interruptions between weeks 3-72 lasting 1-6 weeks: Resume with 2-week loading dose of 200 mg daily 3
- For interruptions >8 weeks: Resume with 2-week loading dose of 400 mg daily 3
Treatment Outcomes
Recent studies show improved outcomes with bedaquiline-containing regimens:
- Treatment success rates of approximately 73% (52.9% cured + 20% completed treatment) 4
- Mortality rates of around 14.2% 4
Combination Therapy Considerations
The combination of bedaquiline with delamanid appears to have no additive QTc-prolonging effects and may be considered for patients with limited treatment options 5
Potential Future Developments
Alternative daily dosing regimens for bedaquiline (200 mg daily for 8 weeks followed by 100 mg daily) are under clinical evaluation to simplify administration 6