What are the criteria for initiating the BPaLM (Bleomycin, Platinol (cisplatin), Adriamycin (doxorubicin), and Leucovorin with Methotrexate) regimen?

Criteria for BPaLM Regimen

The BPaLM regimen (Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin) is indicated for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients who have not had prior exposure to bedaquiline, pretomanid, and linezolid for more than one month. 1

Patient Selection Criteria

Indications:

• Confirmed MDR/RR-TB (multidrug-resistant/rifampicin-resistant tuberculosis)
• Fluoroquinolone-susceptible TB (for BPaLM version)
• Pre-extensively drug-resistant TB (fluoroquinolone-resistant) can use BPaL version (without moxifloxacin)
• Extensive pulmonary TB
• Extrapulmonary TB
• HIV co-infection

Contraindications:

• Extensively drug-resistant TB
• Age < 14 years
• Pregnancy/breastfeeding
• Prior exposure to any of the regimen drugs for ≥30 days
• When resistance to specific drugs with prior exposure must be ruled out before considering the regimen

Monitoring Requirements

• Drug susceptibility testing (DST) to fluoroquinolones is strongly encouraged before starting treatment
• If resistance to fluoroquinolones is documented after starting BPaLM, moxifloxacin should be stopped, and the regimen continued as BPaL
• Close monitoring for patients with:
  • History of cardiac disease or concomitant drugs that prolong QTc
  • Body mass index < 17
  • Hemoglobin < 9 g/dl or platelet count < 75,000/mm³
  • Pre-existing peripheral neuropathy of grade III-IV

Treatment Duration

• Standard duration: 6 months (26 weeks)
• When the regimen is BPaL from the start or is changed to BPaL, it can be extended to a total of 9 months (39 weeks) if sputum cultures remain positive between months 4 and 6

Dosing

• Bedaquiline: Standard dosing
• Pretomanid: Standard dosing
• Linezolid: 600 mg once daily for 26 weeks
• Moxifloxacin: Standard dosing

Important Considerations

The BPaLM regimen is preferred over other regimens (including the 9-month all-oral regimen and the 18-month longer regimen) due to:

• Higher treatment success rates
• Fewer failures or recurrences
• Less emerging drug resistance
• Similar adverse event profile

Common Pitfalls and Caveats

1. Drug Resistance Testing: Failure to perform drug susceptibility testing for fluoroquinolones before starting treatment can lead to inappropriate regimen selection.

2. Prior Drug Exposure: Not assessing prior exposure to bedaquiline, pretomanid, or linezolid can lead to treatment failure if resistance has developed.

3. Monitoring: Inadequate monitoring of patients with risk factors (cardiac disease, low BMI, hematologic abnormalities) can lead to serious adverse events.

4. Regimen Adjustment: Failure to switch from BPaLM to BPaL when fluoroquinolone resistance is detected can compromise treatment efficacy.

5. Treatment Extension: Not extending treatment duration when sputum cultures remain positive between months 4 and 6 can lead to relapse.

The BPaLM regimen represents a significant advancement in MDR/RR-TB treatment, offering a shorter, more effective option with comparable safety to previous longer regimens.