Treatment of Multidrug-Resistant Tuberculosis (MDR TB)

Core Components of MDR TB Treatment

The American Thoracic Society recommends 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, 2
The treatment regimen should include levofloxacin or moxifloxacin (later-generation fluoroquinolones) 1
The regimen may also include cycloserine or terizidone 4
Delamanid, pyrazinamide (if susceptibility confirmed), imipenem-cilastatin or meropenem (with amoxicillin-clavulanate), amikacin or streptomycin (if susceptibility confirmed), and p-aminosalicylic acid may be added to complete the regimen 4, 5, 6

The intensive phase should last 5-7 months after culture conversion 1, 2
The total treatment duration should be 15-21 months after culture conversion 1, 2
For pre-XDR and XDR TB, the treatment duration should be 15-24 months after culture conversion 1, 2

Kanamycin or capreomycin (injectable agents) should not be used 4, 6
Macrolides (azithromycin and clarithromycin) should not be used 4, 5
Amoxicillin-clavulanate alone should not be used (only use with carbapenems) 4, 5
Ethionamide/prothionamide should not be used if more effective drugs are available 4, 5
p-aminosalicylic acid should not be used if more effective drugs are available 4, 5

A 9-12 month shorter regimen may be considered for patients who meet certain criteria, including no previous exposure to second-line TB drugs, no fluoroquinolone resistance, and no extensive pulmonary TB disease or severe extrapulmonary TB 3
Injectable agents should only be considered when susceptibility is confirmed and oral options are limited 4, 6
Carbapenems should always be used with amoxicillin-clavulanate 4, 6

Using fewer than five effective drugs in the intensive phase should be avoided 7, 1
Insufficient treatment duration (less than 15 months after culture conversion) should be avoided 1, 2

For isoniazid-resistant TB (but not MDR), a later-generation fluoroquinolone should be added to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide 4, 5
For contacts of MDR-TB patients, LTBI treatment with a later-generation fluoroquinolone alone or with a second drug based on source-case susceptibility should be considered 6