What are the recommended regimens and doses for adults with drug-resistant Tuberculosis (TB) according to the National Guidelines for Management of Drug Resistant TB published by the National Tuberculosis Elimination Programme (NTEP) in 2024?

Drug-Resistant TB Treatment Regimens for Adults

I cannot provide a summary of the 2024 NTEP India guidelines as they are not included in the evidence provided. However, I can summarize the most current international guidelines for drug-resistant TB treatment in adults based on the available evidence.

Current Recommended Regimens for Drug-Resistant TB

For MDR/RR-TB (Multidrug-Resistant/Rifampicin-Resistant TB)

The treatment landscape has shifted dramatically toward shorter, all-oral regimens with newer agents.

First-Line Option: 6-Month BPaLM Regimen

• Bedaquiline + Pretomanid + Linezolid (600 mg) + Moxifloxacin for 6 months (26 weeks) 1, 2
• This regimen is preferred over longer 9-month or 18-month regimens for eligible patients 1
• Eligibility criteria:
  • MDR/RR-TB with fluoroquinolone susceptibility confirmed 1
  • No prior exposure to bedaquiline or linezolid for >30 days 1
  • Age ≥14 years 1
  • Can be used in HIV co-infected patients 1
  • Contraindications: Pregnancy/breastfeeding, age <14 years 1

Alternative: 6-Month BPaL Regimen (for Pre-XDR-TB)

• Bedaquiline + Pretomanid + Linezolid (600 mg) for 6 months 1, 2
• Used specifically for pre-XDR-TB (fluoroquinolone-resistant MDR-TB) 1
• Can be extended to 9 months (39 weeks) if sputum cultures remain positive between months 4-6 1

Second-Line Option: 9-Month All-Oral Regimen

• Recommended when 6-month regimens cannot be used 1
• Must confirm fluoroquinolone susceptibility 1
• Contraindications: Pre-XDR-TB, extensive pulmonary TB, prior exposure to regimen drugs for >30 days 1
• Can use ethionamide-sparing regimen in pregnancy 1

Third-Line Option: Longer 18-Month Individualized Regimen

• Reserved for cases where shorter regimens cannot be implemented due to:
  • Drug intolerance 1
  • Drug-drug interactions 1
  • Extensively drug-resistant TB 1
  • Extensive extrapulmonary TB 1
  • Previous treatment failure 1

For Pre-XDR and XDR-TB (Extensively Drug-Resistant TB)

Core regimen components 2:

• Bedaquiline (strongly recommended) 2
• Later-generation fluoroquinolone (levofloxacin preferred over moxifloxacin if susceptible) 2
• Linezolid (conditionally recommended) 2
• Clofazimine (conditionally recommended) 2
• Cycloserine or terizidone (conditionally recommended) 2

Treatment duration 2:

• Intensive phase: 5-7 months after culture conversion 2
• Total duration: 15-24 months after culture conversion 2

For Isoniazid-Resistant TB (Rifampin-Susceptible)

• Rifampin + Ethambutol for minimum 12 months 3
• Pyrazinamide may be included if isolate not resistant to it 3

Adult Dosing for Key Anti-TB Drugs

First-Line Drugs (for Drug-Susceptible TB) 1

Drug	Daily Dose (Adults)
Isoniazid	5 mg/kg (typically 300 mg)
Rifampin	10 mg/kg (typically 600 mg)
Pyrazinamide	10-20 mg/kg
Ethambutol	15-20 mg/kg (max 800-1600 mg depending on weight)

• Pyridoxine (Vitamin B6): 25-50 mg/day with isoniazid for all at-risk patients (HIV, diabetes, pregnancy, malnutrition, renal failure, elderly) 1

Second-Line Drugs for MDR-TB 1

WHO Group A (Fluoroquinolones):

• Levofloxacin 1
• Moxifloxacin 1
• Gatifloxacin 1

WHO Group B (Second-line injectables - now less preferred):

• Amikacin 1
• Capreomycin 1
• Kanamycin 1
• Streptomycin 1

WHO Group C (Other second-line agents):

• Ethionamide/Prothionamide 1
• Cycloserine/Terizidone 1
• Linezolid 1
• Clofazimine 1

WHO Group D (Add-on agents):

• D1: Pyrazinamide, Ethambutol, High-dose Isoniazid 1
• D2: Bedaquiline, Delamanid 1
• D3: p-Aminosalicylic acid, Imipenem-cilastatin, Meropenem, Amoxicillin-clavulanate 1

Treatment Construction Principles for MDR-TB

When using 18-month individualized regimens 1:

• Include at least 5 effective drugs during intensive phase 1
• Include pyrazinamide plus 4 core second-line drugs 1
• Select drugs in order: 1 from Group A + 1 from Group B + at least 2 from Group C 1
• If minimum of 5 drugs cannot be achieved from Groups A-C, add from Group D2, then D3 1

Critical Treatment Monitoring

• Monthly sputum cultures until conversion, then less frequently 2
• Directly observed therapy (DOT) strongly recommended 2
• Drug susceptibility testing on first isolate mandatory 3, 2
• Additional DST if cultures remain positive after 3 months 3

Surgical Considerations for XDR-TB

• Elective partial lung resection (lobectomy or wedge resection) may be considered for adults with XDR-TB receiving antimicrobial therapy 2
• Surgery should only be performed by experienced surgeons after several months of intensive chemotherapy 2

Critical Pitfalls to Avoid

• Never add a single drug to a failing regimen - this leads to acquired resistance 3, 2
• Avoid kanamycin and capreomycin - associated with poor outcomes 2
• Do not use fewer than 5 effective drugs in intensive phase for MDR-TB 2
• Do not treat XDR-TB for less than 15 months after culture conversion - higher relapse rates 2
• When initiating therapy for suspected XDR-TB, add at least 2-3 new drugs to which susceptibility can be inferred 2
• Monitor QTc interval closely when combining bedaquiline, moxifloxacin, and clofazimine 1, 4
• Watch for linezolid and cycloserine toxicity - high frequency of serious adverse events 4

Special Populations

HIV Co-infection:

• All regimens can be used in HIV-positive patients 1
• Treatment duration: 9 months minimum, at least 6 months after sputum conversion 3
• Consider rifabutin substitution with appropriate dose adjustments when using protease inhibitors or NNRTIs 3, 5

Pregnancy/Breastfeeding:

• BPaLM/BPaL regimens contraindicated 1
• Use ethionamide-sparing 9-month regimen or 18-month individualized regimen 1

Note: The evidence provided does not contain the specific 2024 NTEP India guidelines requested. The recommendations above are based on the most recent international guidelines (WHO 2022 update, ATS/CDC/ERS/IDSA 2019 and 2025 updates) available in the evidence.