Current Treatment Regimens for Multidrug-Resistant Tuberculosis (MDR-TB)
The current recommended treatment for MDR-TB includes a 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, and moxifloxacin) as the preferred option for patients with fluoroquinolone-susceptible MDR-TB, with alternative options being a 9-month all-oral regimen or longer 18-20 month individualized regimens when shorter regimens cannot be used. 1
First-Line Treatment Options
1. 6-Month BPaLM Regimen (Preferred)
- Composition: Bedaquiline, pretomanid, linezolid (600 mg), and moxifloxacin
- Duration: 6 months
- Indications: MDR/RR-TB with confirmed fluoroquinolone susceptibility 1
- Efficacy: Superior to standard of care with 89% favorable outcomes (vs 51% in standard of care) 1
- Safety: Only 25% of patients experience grade 3/4 adverse events (vs 60% on standard of care) 1
2. 6-Month BPaL Regimen
- Composition: Bedaquiline, pretomanid, and linezolid (600 mg)
- Duration: 6 months (may be extended to 9 months if sputum cultures remain positive between months 4-6) 1
- Indications: Pre-XDR TB (MDR/RR-TB with fluoroquinolone resistance) 1
3. 9-Month All-Oral Regimen
- Composition: Bedaquiline, linezolid (for 2 months), levofloxacin/moxifloxacin, clofazimine, ethambutol, and pyrazinamide 1
- Duration: 9-12 months
- Indications: MDR/RR-TB with confirmed fluoroquinolone susceptibility when 6-month regimen cannot be used 1
- Efficacy: 83% favorable outcomes (STREAM Stage 2 trial) 1
Longer Individualized Regimens (18-20 months)
When shorter regimens cannot be used, longer individualized regimens should include:
Drug Classification and Selection
Group A (include all three): 1, 2
- Bedaquiline (strongly recommended for ≥18 years, conditionally for 6-17 years)
- Linezolid (strongly recommended)
- Fluoroquinolone (levofloxacin or moxifloxacin - strongly recommended)
Group B (add one or both): 1
- Clofazimine (conditional recommendation)
- Cycloserine or terizidone (conditional recommendation)
Group C (add when regimen cannot be composed with Groups A and B): 1
- Ethambutol (conditional recommendation)
- Delamanid (for patients ≥3 years)
- Pyrazinamide (when susceptibility confirmed)
- Imipenem-cilastatin or meropenem (with amoxicillin-clavulanate)
- Amikacin or streptomycin (only when susceptibility confirmed and monitoring available)
- Ethionamide/prothionamide (only if better options not available)
- p-Aminosalicylic acid (only if better options not available)
Duration Guidelines
- Total treatment duration: 18-20 months for most patients 1, 2
- Post-culture conversion: 15-17 months after culture conversion 1, 2
Contraindications and Drugs to Avoid
- Do not use: 1
- Kanamycin and capreomycin (strong recommendation against)
- Amoxicillin-clavulanate (except when providing clavulanate with carbapenems)
- Macrolides (azithromycin and clarithromycin)
- Clavulanic acid alone
Special Populations and Considerations
Patient Selection for Different Regimens
| Patient Characteristics | 6-Month BPaLM/BPaL | 9-Month All-Oral | Longer 18-Month |
|---|---|---|---|
| Fluoroquinolone-resistant TB | BPaL only | No | Yes |
| Extensively DR-TB | No | No | Yes |
| Extensive pulmonary TB | Yes | No | Yes |
| Age <14 years | No | Yes | Yes |
| Pregnant/breastfeeding | No | Yes (ethionamide-sparing) | Yes |
| Prior exposure to regimen drugs >30 days | No | No | Yes |
Monitoring Requirements
- Culture monitoring: Monthly sputum cultures recommended to monitor treatment response 1
- ECG monitoring: After initial 2 weeks of bedaquiline therapy and then monthly for QT interval prolongation 2
- Blood levels: Weekly for patients receiving cycloserine >500 mg daily or those with reduced renal function 3
- Electrolytes: Regular monitoring of serum calcium, magnesium, and potassium 2
Common Pitfalls and Caveats
Drug resistance testing: Ideally, all MDR-TB patients should have susceptibility testing for fluoroquinolones, bedaquiline, and linezolid before starting treatment 4. However, capacity for drug susceptibility testing is often insufficient in resource-limited settings.
QT interval prolongation: The combination of bedaquiline, moxifloxacin, and clofazimine in the same regimen may excessively increase the QT interval 4. Consider using levofloxacin instead of moxifloxacin when using bedaquiline and clofazimine together.
Adverse effects management: Linezolid and cycloserine have high frequencies of serious adverse events 4. For linezolid, monitor for peripheral neuropathy, optic neuritis, and myelosuppression. For cycloserine, monitor for CNS toxicity, especially at doses >500 mg daily 3.
Drug interactions: Concurrent administration of ethionamide with cycloserine may potentiate neurotoxic side effects 3. Alcohol and cycloserine are incompatible, especially at higher doses.
Resistance amplification: Risk of acquired bedaquiline resistance is significant, especially in patients with undetected resistance to fluoroquinolones 4. Ensure proper drug susceptibility testing when available.
The evolution of MDR-TB treatment has dramatically improved outcomes in recent years, with shorter, more effective, and less toxic regimens becoming available. The shift from injectable-containing regimens to all-oral options has significantly reduced adverse events while maintaining or improving efficacy 5.