Recommended Longer Oral Regimen for Drug-Resistant Tuberculosis (DR-TB)

Core Components of the Longer Oral Regimen

The American Thoracic Society recommends a longer oral regimen for drug-resistant tuberculosis (DR-TB) that includes 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, 2, 3
Bedaquiline is strongly recommended for inclusion in all longer MDR-TB regimens for patients ≥18 years (strong recommendation) 2, 3
A later-generation fluoroquinolone, either levofloxacin or moxifloxacin, is recommended (strong recommendation) 1, 2
Linezolid should be included in the treatment regimen (strong recommendation) 2, 4

Clofazimine is suggested for inclusion in longer MDR-TB regimens (conditional recommendation) 1, 2
Cycloserine is suggested for inclusion in longer MDR-TB regimens (conditional recommendation) 1, 2
Pyrazinamide may be included when the M. tuberculosis isolate has not been found resistant to it (conditional recommendation) 1, 2
Delamanid may be included for patients aged ≥3 years (conditional recommendation) 1, 5

Amoxicillin-clavulanate is not recommended except when the patient is receiving a carbapenem (strong recommendation) 5, 6
Macrolides (azithromycin and clarithromycin) are not recommended (strong recommendation) 5, 6
Ethionamide/prothionamide is not recommended if more effective drugs are available (conditional recommendation) 5, 6
p-aminosalicylic acid is not recommended if more effective drugs are available (conditional recommendation) 5, 6
Kanamycin and capreomycin are not recommended for inclusion in regimens (conditional recommendation) 1, 3

Amikacin or streptomycin may be included only when susceptibility is confirmed and no better options exist (conditional recommendation) 1, 2

Total treatment duration is 15-24 months after culture conversion for MDR-TB 1, 2

Sputum culture should be performed in addition to sputum smear microscopy monthly to monitor treatment response 4

For patients with HIV co-infection, antiretroviral therapy should be started as early as possible (within the first 8 weeks) following initiation of anti-TB treatment 4
Elective partial lung resection (lobectomy or wedge resection) may be considered alongside the recommended MDR-TB regimen in appropriate cases 4

Never add a single drug to a failing regimen as this leads to acquired resistance 7
Do not use standardized shorter regimens that include drugs for which there is documented or high likelihood of resistance 1
Avoid using injectable agents when possible due to their toxicity profile and availability of effective oral alternatives 3
Ensure adherence to the full regimen through appropriate support measures to prevent relapse and development of additional drug resistance 4

Health education and counseling should be provided to all patients on TB treatment 4
Consider treatment adherence interventions such as digital medication monitoring, material support, and psychological support 4