BPaLM Regimen for Drug-Resistant TB

Introduction and Rationale

BPaLM is a 6-month (24-week), entirely oral, four-drug combination regimen utilized for Multidrug-Resistant Tuberculosis (MDR-TB) and Rifampicin-Resistant TB (RR-TB).
Replaces historically prolonged 18 to 24-month regimens that mandated toxic, daily injectable aminoglycosides causing irreversible sensorineural hearing loss.
Highly effective, achieving an 89% clinical success rate in the TB-PRACTECAL phase 3 trial compared to a 52% success rate with older standards of care.

Drug	Mechanism of Action	Key Characteristics
Bedaquiline (Bdq)	Targets mycobacterial ATP synthase, effectively starving the bacteria of cellular energy.	First-in-class diarylquinoline; highly effective against replicating and dormant bacilli.
Pretomanid (Pa)	Inhibits mycolic acid biosynthesis under aerobic conditions and generates reactive nitrogen species under anaerobic conditions.	Novel nitroimidazooxazine antimicrobial.
Linezolid (Lzd)	Inhibits mycobacterial protein synthesis by binding to 23S ribosomal RNA.	Requires close vigilance due to time- and dose-dependent mitochondrial toxicities.
Moxifloxacin (Mfx)	Inhibits DNA gyrase and topoisomerase IV enzymes, arresting DNA replication.	Dropped from the regimen if fluoroquinolone resistance is present, leaving the BPaL regimen.

Inclusion: The WHO and NTEP guidelines strongly recommend BPaLM as the primary treatment of choice, explicitly extending this to adolescents aged 14 years and older.
Age Restriction: Currently not approved for children under 14 years; trials like IMPAACT 2034 and BEAT-India are actively investigating Pretomanid pharmacokinetics for younger pediatric cohorts.
Exclusion Criteria:
- Severe forms of extrapulmonary TB, specifically TB meningitis, osteoarticular TB, or disseminated/miliary TB with multiorgan involvement.
- Pregnant or breastfeeding adolescents.
- Patients with prior exposure exceeding one month to Bedaquiline, Linezolid, or Pretomanid/Delamanid without explicit drug susceptibility testing confirming ongoing sensitivity.

All medications are administered orally under Directly Observed Treatment (DOT) for exactly 26 weeks (6 months).
Bedaquiline: Loading dose of 400 mg once daily for the first 14 days, followed by a maintenance dose of 200 mg three times per week.
Pretomanid: 200 mg once daily.
Linezolid: Initiated at 600 mg once daily. Dose is reduced to 300 mg daily if severe myelosuppression or neuropathy develops.
Moxifloxacin: 400 mg once daily.
Adjunctive Therapy: Mandatory co-administration of Pyridoxine (Vitamin B6) at 50-100 mg daily for the entire duration to proactively mitigate Linezolid-induced peripheral neuropathy.

Monitoring Domain	Protocol and Intervention
Cardiovascular	Baseline ECG is mandatory. Both Bedaquiline and Moxifloxacin prolong the QT interval. Withhold drugs and correct electrolytes if QTcF exceeds 500 ms.
Hematological and Neurological	Baseline and monthly Complete Blood Count (CBC) required. Clinical screening for peripheral/optic neuropathy at every visit. Reduce Linezolid dose if toxicity manifests.
Hepatic	Baseline and monthly Liver Function Tests (LFTs). Interrupt therapy if transaminases rise above 5 times the upper limit of normal.
Microbiological	Sputum smear microscopy and liquid mycobacterial culture performed monthly from month 3 onwards. Cure declared after full 6 months completion with at least three consecutive negative cultures.