Drug-resistant tuberculosis

Red Flags

Bedaquiline + linezolid + clofazimine — QTc monitoring at baseline, week 2, then monthly; pause if QTcF >500 ms^[2]
Linezolid peripheral neuropathy or optic neuropathy — dose reduction or substitution; may persist after stopping^[2]
Pre-XDR TB (MDR + fluoroquinolone resistance) and XDR TB — specialist PMDT centre; complex individualised regimens^[2]
Hepatitis on DR-TB regimen — ALT >3× ULN with symptoms or >5× without — pause regimen; sequential reintroduction under specialist^[2]

Programmatic Management of Drug-Resistant TB (PMDT)^[2]
All DR-TB managed under PMDT centres with directly observed treatment, structured monitoring, and comorbidity management. Drugs procured free at point of care under NTEP
Active drug safety monitoring^[2]
Monthly clinical review, monthly LFTs, quarterly TSH, monthly QTc on bedaquiline, baseline + 3-monthly visual acuity on linezolid

Drug	Class	Adult	Paediatric	Notes
Bedaquiline + pretomanid + linezolid (BPaL)^[2]	All-oral 6-month MDR/pre-XDR-TB regimen	Bedaquiline 400 mg PO daily × 14 days then 200 mg three times weekly × 22 weeks; pretomanid 200 mg PO once daily × 26 weeks; linezolid 600 mg PO once daily × 26 weeks (dose reduce for toxicity)	Per package paediatric dosing where approved	First-line shorter all-oral regimen for MDR/pre-XDR per WHO 2024; replaces 18-month conventional regimens in eligible patients
Bedaquiline + pretomanid + linezolid + moxifloxacin (BPaLM)^[2]	All-oral 6-month MDR-TB regimen with FQ	Add moxifloxacin 400 mg PO daily to BPaL	—	Preferred for MDR-TB without FQ resistance; per ZeNix and TB-PRACTECAL
Conventional longer all-oral regimen^[2]	Individualised 18-month regimen	Bedaquiline + linezolid + levofloxacin + cycloserine + clofazimine (variable per DST)	Per weight band	When BPaL/BPaLM not feasible (drug intolerance, comorbidity, pregnancy, paediatric); duration 18 months minimum
Pyridoxine and clofazimine (adjuncts)^[2]	Vitamin / antitubercular adjunct	Pyridoxine 50 mg PO daily; clofazimine 100 mg PO daily	Per weight	Pyridoxine prevents linezolid neuropathy; clofazimine part of conventional regimens

Bedaquiline + pretomanid + linezolid (BPaL)^[2]

All-oral 6-month MDR/pre-XDR-TB regimen

Adult: Bedaquiline 400 mg PO daily × 14 days then 200 mg three times weekly × 22 weeks; pretomanid 200 mg PO once daily × 26 weeks; linezolid 600 mg PO once daily × 26 weeks (dose reduce for toxicity)
Paediatric: Per package paediatric dosing where approved

First-line shorter all-oral regimen for MDR/pre-XDR per WHO 2024; replaces 18-month conventional regimens in eligible patients

Bedaquiline + pretomanid + linezolid + moxifloxacin (BPaLM)^[2]

All-oral 6-month MDR-TB regimen with FQ

Preferred for MDR-TB without FQ resistance; per ZeNix and TB-PRACTECAL

Conventional longer all-oral regimen^[2]

Individualised 18-month regimen

Adult: Bedaquiline + linezolid + levofloxacin + cycloserine + clofazimine (variable per DST)
Paediatric: Per weight band

When BPaL/BPaLM not feasible (drug intolerance, comorbidity, pregnancy, paediatric); duration 18 months minimum

Pyridoxine and clofazimine (adjuncts)^[2]

Vitamin / antitubercular adjunct

Pyridoxine prevents linezolid neuropathy; clofazimine part of conventional regimens

Take all DR-TB drugs daily under DOT — interruption causes resistance amplification and treatment failure^[2]
Watch for jaundice, dizziness, vision changes, numb hands/feet, palpitations, severe vomiting — same-day medical review^[2]
Avoid alcohol throughout treatment; tell other clinicians about your DR-TB therapy — many drug interactions^[2]

Rifampicin-resistant TB on XpertPMDT centre — initiate BPaL/BPaLM after extended DST^[2]
Pre-XDR or XDR TBSpecialist PMDT centre with extended-DST capability^[2]
Severe ATT-related adverse event (hepatitis, optic neuropathy, prolonged QTc)Hospital admission; sequential reintroduction or regimen modification^[2]

Management of MDR/pre-XDR/XDR TB with all-oral shorter regimens (BPaL/BPaLM); programmatic treatment under PMDT.

1.NTEP Guidelines on Programmatic Management of Drug-Resistant TB (2024); WHO Consolidated Guidelines on TB: Drug-Resistant TB Treatment (2024 update) (2024)
2.NTEP Guidelines on Programmatic Management of Drug-Resistant TB; WHO Consolidated Guidelines on TB: Drug-Resistant TB Treatment, 2024 Update. NTEP / WHO (2024)