What is the BPaLM (Bedaquiline, Pretomanid, Linezolid, and potentially other drugs like Amoxicillin/Clavulanate) regimen for TB treatment?

BPaLM Regimen for Drug-Resistant Tuberculosis

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) due to superior treatment success rates and reduced risk of treatment failure compared to longer regimens. 1

Components and Dosing

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 (preferred dosage)
• Moxifloxacin: Standard dose daily

For patients with fluoroquinolone resistance, the BPaL regimen (without moxifloxacin) is used instead 1.

Treatment Duration and Administration

• Standard treatment duration is 6 months (26 weeks)
• Medications should be taken with food
• If fluoroquinolone resistance is detected after starting BPaLM, moxifloxacin should be discontinued and the regimen continued as BPaL 1
• Missed doses can be made up at the end of treatment, except for linezolid doses missed due to adverse reactions 2

Patient Selection

Appropriate for:

• MDR/RR-TB patients without fluoroquinolone resistance
• Patients with pre-extensively drug-resistant TB (fluoroquinolone-resistant) can receive BPaL
• Most extrapulmonary TB cases
• People living with HIV 1

Not appropriate for:

• Extensively drug-resistant TB
• Children under 14 years of age
• Pregnant or breastfeeding women
• TB involving the central nervous system, miliary TB, or osteoarticular TB
• Patients with prior exposure (>1 month) to bedaquiline, pretomanid, or linezolid unless resistance is ruled out 1, 2
• Drug-sensitive TB
• Latent TB infection 2

Efficacy

The BPaLM recommendation is based on clinical trials demonstrating:

• 90% favorable outcomes at 6 months after treatment completion in the Nix-TB trial 3
• Higher treatment success rates compared to conventional regimens 4
• Fewer treatment failures or recurrences 1
• Less emerging drug resistance 1

In a comparative study, the BPaL regimen showed significantly better outcomes than conventional bedaquiline-linezolid combination regimens (89.9% vs. 65.1% favorable outcomes) 4.

Adverse Events and Monitoring

Common adverse events requiring monitoring include:

1. Linezolid-related toxicities:

   • Peripheral neuropathy (up to 81% of patients) 3
   • Myelosuppression (48% of patients) 3
   • Optic neuropathy (9% with 1200mg dosing) 5

2. Bedaquiline-related:

   • QTc prolongation (requires ECG monitoring) 6, 1

Monitoring recommendations:

• ECGs after initial 2 weeks of therapy and then monthly
• Monitor serum electrolytes (calcium, magnesium, potassium)
• Close monitoring for patients with BMI <17 1
• Consider linezolid dose reduction to 300 mg daily if toxicity develops, though 600 mg is preferred 1, 5

Alternative Regimens

For patients who cannot receive BPaLM:

• 9-month all-oral bedaquiline-containing regimen (for fluoroquinolone-susceptible cases)
• 18-month longer individualized regimens (for extensively drug-resistant TB) 1

Important Considerations

• Drug susceptibility testing for fluoroquinolones is strongly encouraged but should not delay treatment initiation 1
• If resistance to bedaquiline, linezolid, or pretomanid is confirmed or suspected, the BPaLM/BPaL regimen should be stopped 1
• Patients should avoid alcohol and hepatotoxic medications during treatment 2
• The ZeNix trial showed that linezolid at 600 mg for 26 weeks provided the best risk-benefit ratio with fewer adverse events and dose modifications while maintaining efficacy 5

The BPaLM/BPaL regimen represents a significant advancement in MDR-TB treatment, offering a shorter, all-oral regimen with improved outcomes compared to conventional longer treatments.