BPaLM Regimen for MDR-TB
The BPaLM regimen (Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin) is strongly recommended as the preferred 6-month treatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) over longer regimens, based on superior treatment success rates and reduced risk of treatment failure or recurrence. 1
Composition and Duration
The BPaLM regimen consists of:
- Bedaquiline: 400 mg once daily for 2 weeks, followed by 200 mg three times weekly
- Pretomanid: 200 mg once daily
- Linezolid: 600 mg once daily for 26 weeks (preferred dosage)
- Moxifloxacin: Standard dose daily
Treatment duration is standardized to 6 months (26 weeks) for the complete regimen. If fluoroquinolone resistance is detected after starting BPaLM, moxifloxacin should be discontinued and the regimen continued as BPaL (without moxifloxacin) 1. For BPaL regimens, extension to 9 months (39 weeks) may be considered if sputum cultures remain positive between months 4 and 6 1.
Indications and Patient Selection
BPaLM is indicated for:
- MDR/RR-TB patients without fluoroquinolone resistance
- Patients with pre-extensively drug-resistant TB (fluoroquinolone-resistant) can receive BPaL (without moxifloxacin)
- Patients with extensive pulmonary TB
- Most extrapulmonary TB (except CNS, miliary, and osteoarticular TB)
- People living with HIV
The regimen is not appropriate for:
- Patients with extensively drug-resistant TB
- Children under 14 years of age
- Pregnant or breastfeeding women
- Patients with TB involving the central nervous system, miliary TB, or osteoarticular TB
- Patients with prior exposure (>1 month) to bedaquiline, pretomanid, or linezolid unless resistance to these drugs is ruled out 1
Evidence Base and Rationale
The BPaLM recommendation is based on the TB-PRACTECAL and ZeNix randomized controlled trials, which demonstrated:
- Higher treatment success rates
- Fewer treatment failures or recurrences
- Less emerging drug resistance
- Manageable adverse events profile compared to longer regimens 1
Recent real-world data from Belarus and Uzbekistan confirms these findings, showing 95.3% treatment success in non-trial settings for MDR/RR-TB patients treated with BPaLM 2.
Monitoring and Management of Adverse Events
Common adverse events requiring monitoring:
Linezolid-related:
Bedaquiline-related:
- QTc prolongation (requires ECG monitoring)
- Patients with cardiac disease or taking other QTc-prolonging medications require close monitoring 1
General considerations:
- Patients with BMI <17 require close monitoring
- Those with pre-existing peripheral neuropathy (grade III-IV) or low hemoglobin/platelet counts may benefit from linezolid-sparing regimens 1
Important Clinical Considerations
- Drug susceptibility testing for fluoroquinolones is strongly encouraged but should not delay treatment initiation 1
- Missed doses should be avoided; 26 weeks of prescribed doses should be completed within an overall period of 7 months 1
- If resistance to bedaquiline, linezolid, or pretomanid is confirmed or suspected, the BPaLM/BPaL regimen should be stopped, and patients referred for a longer individualized regimen 1
- Pretomanid is only FDA-approved for use in combination with bedaquiline and linezolid, not as part of other regimens 4
- Directly observed therapy (DOT) is recommended for administration of the complete regimen 4
Alternative Regimens
For patients who cannot receive BPaLM, alternatives include:
- 9-month all-oral bedaquiline-containing regimen (for fluoroquinolone-susceptible cases)
- 18-month longer individualized regimens (for extensively drug-resistant TB or when shorter regimens cannot be used) 1
Research is ongoing to develop modifications to the regimen that may reduce toxicity, such as replacing linezolid with inhaled spectinamides, though these are not yet approved for clinical use 5.