Treatment of Multidrug-Resistant Tuberculosis (MDR TB)
The recommended treatment for MDR TB includes a regimen of at least five effective drugs in the intensive phase and four drugs in the continuation phase, with strong recommendations to include bedaquiline and a later-generation fluoroquinolone (levofloxacin or moxifloxacin) as core drugs. 1
Core Components of MDR TB Treatment
Recommended Drug Selection (Priority Groups)
Group A (Include all when possible): 1
- Levofloxacin or moxifloxacin (later-generation fluoroquinolones)
- Bedaquiline
- Linezolid
Group B (Add one or both): 1
- Clofazimine
- Cycloserine or terizidone
Group C (Add to complete regimen when drugs from Groups A and B cannot be used): 1
- Ethambutol
- Delamanid
- Pyrazinamide (if susceptibility confirmed)
- Imipenem-cilastatin or meropenem (with amoxicillin-clavulanate)
- Amikacin or streptomycin (if susceptibility confirmed)
- Ethionamide or prothionamide
- p-aminosalicylic acid
Treatment Duration
- Intensive phase: 5-7 months after culture conversion 1
- Total treatment duration: 15-21 months after culture conversion 1
- For pre-XDR and XDR TB: 15-24 months after culture conversion 1
Drugs NOT Recommended
- Kanamycin or capreomycin (injectable agents) 1
- Macrolides (azithromycin and clarithromycin) 1
- Amoxicillin-clavulanate alone (only use with carbapenems) 1
- Ethionamide/prothionamide if more effective drugs are available 1
- p-aminosalicylic acid if more effective drugs are available 1
Special Considerations
Shorter All-Oral Regimen Option
A 9-12 month shorter regimen may be considered for patients who: 1
- Have no previous exposure to second-line TB drugs >1 month
- Have no fluoroquinolone resistance
- Have no extensive pulmonary TB disease or severe extrapulmonary TB
- Are not pregnant
- Are >6 years of age
This shorter regimen typically includes: 1
- Bedaquiline (6 months)
- Levofloxacin/moxifloxacin
- Clofazimine
- Pyrazinamide
- Ethambutol
- High-dose isoniazid
- Ethionamide
Injectable Agents
- Only consider amikacin or streptomycin when susceptibility is confirmed and oral options are limited 1
- Always use carbapenems with amoxicillin-clavulanate 1
Treatment Efficacy Considerations
- Including more potentially effective drugs (at least 6) is associated with a 36% greater likelihood of sputum culture conversion 2
- Pyrazinamide inclusion (when susceptible) doubles the likelihood of sputum culture conversion 2
- Including drugs to which baseline DST indicates susceptibility increases treatment success 2, 3
Monitoring and Management
- Implement active Tuberculosis Drug Safety Monitoring (aDSM) due to frequent adverse effects 1, 4
- Monitor for specific toxicities: 4
- Fluoroquinolones: QT prolongation
- Linezolid: peripheral neuropathy, bone marrow suppression
- Bedaquiline: QT prolongation
- Cycloserine: neuropsychiatric effects
- Injectable agents: nephrotoxicity, ototoxicity
Common Pitfalls to Avoid
- Using fewer than five effective drugs in the intensive phase 1
- Combining bedaquiline, moxifloxacin, and clofazimine without QT interval monitoring (risk of excessive QT prolongation) 5
- Inadequate drug susceptibility testing before treatment initiation 5
- Insufficient treatment duration (less than 15 months after culture conversion) 1
- Poor adherence monitoring, which increases risk of further resistance development 6, 5
Special Populations
- For isoniazid-resistant TB (but not MDR): Add a later-generation fluoroquinolone to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide 1
- For contacts of MDR-TB patients: Consider LTBI treatment with a later-generation fluoroquinolone alone or with a second drug based on source-case susceptibility 1