Treatment of Rifampicin-Resistant Mycobacterium Tuberculosis (MTB/RIF)
For rifampicin-resistant tuberculosis, a regimen consisting of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) for 6 months is recommended as the first-line treatment due to superior efficacy and safety compared to longer regimens.
First-Line Treatment Options
6-Month BPaLM Regimen (Preferred)
- The 6-month all-oral BPaLM regimen has demonstrated superior outcomes with significantly fewer unfavorable outcomes compared to standard care (12% vs 41%) 1
- This regimen includes:
- Bedaquiline
- Pretomanid
- Linezolid (600 mg)
- Moxifloxacin
9-Month All-Oral Regimen (Alternative)
- For patients in whom fluoroquinolone resistance has been excluded 2
- Typically includes:
- Bedaquiline (for 6 months)
- Levofloxacin or moxifloxacin
- Clofazimine
- Ethambutol
- Pyrazinamide
- High-dose isoniazid (first 4 months)
Longer Regimen (15-21 months) When Shorter Regimens Cannot Be Used
When shorter regimens are contraindicated due to drug intolerance, drug-drug interactions, extensively drug-resistant TB, or previous treatment failure 2, construct a regimen with at least 5 drugs in the intensive phase and 4 drugs in the continuation phase 2:
Core Drugs (Strong Recommendations)
- Bedaquiline (strong recommendation) 2
- Later-generation fluoroquinolone - levofloxacin or moxifloxacin (strong recommendation) 2
Additional Drugs (Conditional Recommendations)
- Linezolid (conditional recommendation) 2
- Clofazimine (conditional recommendation) 2
- Cycloserine (conditional recommendation) 2
Supplementary Drugs (If Needed)
- Pyrazinamide (if susceptible) 2
- Ethambutol (only when other more effective drugs cannot be assembled) 2
- Amikacin or streptomycin (when susceptibility is confirmed) 2
- Carbapenem with amoxicillin-clavulanate 2
Treatment Duration
- For the BPaLM regimen: 24 weeks (6 months) 1
- For the 9-month all-oral regimen: 9-12 months 2
- For longer regimens:
Monitoring During Treatment
- Monthly bacteriological evaluation during the first 4 months
- Regular assessment for adverse effects:
- Linezolid: Monitor for anemia, peripheral neuropathy, and optic neuritis
- Bedaquiline and clofazimine: ECG monitoring for QT prolongation
- Moxifloxacin: Monitor for QT prolongation and tendinopathy
Drugs to Avoid
- Kanamycin or capreomycin (associated with higher rates of treatment failure and relapse) 2
- Macrolides (azithromycin and clarithromycin) 2
- Amoxicillin-clavulanate (except when used with carbapenems) 2
- Ethionamide/prothionamide (if more effective drugs are available) 2
- p-aminosalicylic acid (if more effective drugs are available) 2
Special Considerations
- The BPaLM regimen has shown a better safety profile with fewer grade 3 or higher adverse events compared to standard care (19% vs 59%) 3
- Drug susceptibility testing for fluoroquinolones, bedaquiline, and linezolid should ideally be performed before starting treatment 4
- For patients with extensive pulmonary TB or extrapulmonary TB (except TB involving central nervous system, miliary TB, and osteoarticular TB), the 6-month BPaLM regimen is now recommended 2
Pitfalls and Caveats
- Inadequate drug susceptibility testing may lead to undetected resistance and treatment failure
- The risk of acquired bedaquiline resistance is higher in patients with undetected fluoroquinolone resistance 4
- The combination of bedaquiline, moxifloxacin, and clofazimine may excessively increase the QT interval, requiring careful ECG monitoring 4
- Linezolid toxicity (peripheral neuropathy, anemia, thrombocytopenia) often requires dose adjustment or discontinuation
The treatment of rifampicin-resistant TB has evolved significantly, with shorter, all-oral regimens now showing superior outcomes to traditional longer regimens. The 6-month BPaLM regimen represents a major advancement in MDR/RR-TB treatment, offering improved efficacy, shorter duration, and better tolerability.