Recommended Longer Oral Regimen for Drug-Resistant Tuberculosis (DR-TB)
The recommended longer oral regimen for drug-resistant tuberculosis (DR-TB) should include bedaquiline, a later-generation fluoroquinolone (levofloxacin or moxifloxacin), and linezolid as core drugs, with additional agents such as clofazimine and cycloserine to construct a regimen with at least five effective drugs. 1
Core Components of the Longer Oral Regimen
Group A Drugs (Include All When Possible):
- Bedaquiline - Strongly recommended for inclusion in all longer MDR-TB regimens for patients ≥18 years (strong recommendation) 1
- May also be included for patients aged 6-17 years (conditional recommendation) 1
- Later-generation fluoroquinolone - Either levofloxacin or moxifloxacin (strong recommendation) 1
- Linezolid - Should be included in the treatment regimen (strong recommendation) 1
Group B Drugs (Add Both When Group A Cannot Be Fully Utilized):
- Clofazimine - Suggested for inclusion in longer MDR-TB regimens (conditional recommendation) 1
- Cycloserine - Suggested for inclusion in longer MDR-TB regimens (conditional recommendation) 1
Additional Agents to Consider:
- Pyrazinamide - May be included when the M. tuberculosis isolate has not been found resistant to it (conditional recommendation) 1
- Ethambutol - Should only be included when other more effective drugs cannot be assembled to achieve a total of five drugs in the regimen (conditional recommendation) 1
- Delamanid - May be included for patients aged ≥3 years (conditional recommendation) 1
Drugs NOT Recommended for Inclusion:
- Amoxicillin-clavulanate - Not recommended except when the patient is receiving a carbapenem (strong recommendation) 1
- Macrolides (azithromycin and clarithromycin) - Not recommended (strong recommendation) 1
- Ethionamide/prothionamide - Not recommended if more effective drugs are available (conditional recommendation) 1
- p-aminosalicylic acid - Not recommended if more effective drugs are available (conditional recommendation) 1
- Kanamycin and capreomycin - Not recommended for inclusion in regimens (conditional recommendation) 1
Injectable Agents (Only When Necessary):
- Amikacin or streptomycin - May be included only when susceptibility is confirmed and no better options exist (conditional recommendation) 1
- Carbapenem (always with amoxicillin-clavulanate) - May be included when necessary (conditional recommendation) 1
Treatment Duration:
- Total treatment duration: 15-24 months after culture conversion for MDR-TB 1
- For pre-XDR and XDR-TB: 15-24 months after culture conversion 1, 2
Monitoring Treatment Response:
- Perform sputum culture in addition to sputum smear microscopy monthly to monitor treatment response 1
- Regular clinical assessment for symptom improvement and adverse effects 3
Special Considerations:
- HIV co-infection: Antiretroviral therapy should be started for all patients with HIV and DR-TB, regardless of CD4 count, as early as possible (within the first 8 weeks) following initiation of anti-TB treatment 1
- Surgery: Elective partial lung resection (lobectomy or wedge resection) may be considered alongside the recommended MDR-TB regimen in appropriate cases 1
Common Pitfalls to Avoid:
- Never add a single drug to a failing regimen as this leads to acquired resistance 3
- Do not use standardized shorter regimens that include drugs for which there is documented or high likelihood of resistance 1, 2
- Avoid using injectable agents when possible due to their toxicity profile and availability of effective oral alternatives 1, 2
- Ensure adherence to the full regimen through appropriate support measures to prevent relapse and development of additional drug resistance 1, 3
Treatment Support:
- Health education and counseling should be provided to all patients on TB treatment 1
- Consider treatment adherence interventions such as digital medication monitoring, material support, and psychological support 1
The evolution of DR-TB treatment has moved toward all-oral regimens with newer and repurposed drugs that have shown improved efficacy and reduced toxicity compared to older injectable-containing regimens 4, 2. This approach prioritizes patient outcomes in terms of reduced morbidity, mortality, and improved quality of life.