What is the recommended empirical antitubercular (anti-tuberculosis) drug regimen for a 9-month treatment?

Empirical Antitubercular Drug Extended 9-Month Regimen

The recommended empirical 9-month antitubercular drug regimen consists of an intensive phase with at least five effective drugs for 4 months (including bedaquiline, fluoroquinolone, clofazimine, ethambutol, high-dose isoniazid, and either ethionamide or linezolid), followed by a 5-month continuation phase with fluoroquinolone, clofazimine, ethambutol, and pyrazinamide. 1

Intensive Phase (First 4 Months)

• The intensive phase should include at least five effective TB medicines to reduce the risk of treatment failure and development of further drug resistance 1

• The recommended 9-month all-oral regimen consists of:

  • Bedaquiline (for 6 months total)
  • Fluoroquinolone (levofloxacin or moxifloxacin)
  • Clofazimine
  • Ethambutol
  • High-dose isoniazid
  • Pyrazinamide
  • Plus either ethionamide OR linezolid (600mg daily, maximum 2 months) 1

• The intensive phase may be extended to 6 months if bacteriological conversion is not seen at the end of the fourth month of treatment 1

Continuation Phase (5 Months)

• After completing the intensive phase, treatment continues with:
  • Fluoroquinolone
  • Clofazimine
  • Ethambutol
  • Pyrazinamide 1

Special Considerations

• This 9-month regimen is the preferred treatment option over longer regimens for patients without previous exposure to second-line treatment (including bedaquiline) 1
• For patients with extensive pulmonary disease, severe extrapulmonary TB, CNS, miliary, or osteoarticular TB, longer treatment (18-20 months) is still recommended 1
• For pregnant and lactating women, the 9-month regimen with linezolid is recommended instead of ethionamide due to contraindication of ethionamide in pregnancy 1
• For children of all ages, the 9-month all-oral regimen can be used, whereas the shorter BPaLM regimen is not recommended in children under 14 years 1

Drug Selection Considerations

• When choosing a fluoroquinolone, levofloxacin is often preferred over moxifloxacin due to moxifloxacin's higher potential for cardiotoxicity, although both have similar efficacy 1
• If pyrazinamide cannot be used (due to resistance or toxicity), an additional agent from WHO groups C or D can be added to strengthen the regimen 1
• The choice between ethionamide and linezolid variations should be based on patient factors, with linezolid preferred in pregnant women 1

Monitoring During Treatment

• Directly observed therapy (DOT) is recommended to ensure adherence to the regimen 1
• Regular monitoring of bacteriology (sputum smear and culture) is essential to assess treatment response 1
• Drug toxicity monitoring should be performed according to international recommendations to limit the probability of losing an effective drug due to adverse events 1

Important Caveats

• The 9-month regimen should not be used in cases with:

  • Confirmed resistance to fluoroquinolones
  • Previous exposure to second-line drugs for more than 1 month
  • Intolerance to any of the medicines in the regimen
  • Unavailability of any medicine in the regimen 1

• Treatment decisions for drug-resistant TB should ideally be made by a team of experts rather than individual physicians to minimize errors and share expertise 1

• Never add only one effective drug to a failing regimen, as this can lead to development of further drug resistance 1

• If the patient is not responding to treatment, consultation with a TB expert is strongly recommended 1

This 9-month regimen represents a significant improvement over older, longer regimens for drug-resistant TB, offering a more manageable treatment duration while maintaining efficacy when used in appropriate patients.