Treatment Approach for Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis

Diagnosis and Drug Susceptibility Testing

The American Thoracic Society recommends drug susceptibility testing (DST) should be performed on the first isolate from all patients with TB to guide appropriate treatment selection 4
Only drugs to which the patient's M. tuberculosis isolate has documented or high likelihood of susceptibility should be included in the treatment regimen 5, 6

The American College of Chest Physicians recommends including a later-generation fluoroquinolone (levofloxacin or moxifloxacin) as a cornerstone of the regimen (strong recommendation) 3
The American College of Chest Physicians recommends including bedaquiline in the regimen (strong recommendation) 3
The American College of Chest Physicians recommends including linezolid in the regimen (conditional recommendation) 3
The American College of Chest Physicians recommends including clofazimine in the regimen (conditional recommendation) 3
The American College of Chest Physicians recommends including cycloserine in the regimen (conditional recommendation) 3
Pyrazinamide should be included only when the M. tuberculosis isolate has not been found resistant to it (conditional recommendation) 3
Ethambutol should be included only when other more effective drugs cannot be assembled to achieve a total of five drugs in the regimen (conditional recommendation) 3
Injectable agents: If needed, amikacin or streptomycin may be included when susceptibility is confirmed, but kanamycin and capreomycin should NOT be used (conditional recommendation) 1, 2
Carbapenems (always used with amoxicillin-clavulanic acid) may be included if needed to compose an effective regimen (conditional recommendation) 1, 2

The American College of Chest Physicians recommends an intensive phase of 5-7 months after culture conversion (conditional recommendation) 3
The American College of Chest Physicians recommends a total treatment duration of 15-21 months after culture conversion for MDR-TB (conditional recommendation) 3
For XDR-TB, the American College of Chest Physicians recommends a total treatment duration of 15-24 months after culture conversion (conditional recommendation) 3

Elective partial lung resection (lobectomy or wedge resection) may be considered for adults with MDR-TB receiving antimicrobial therapy (conditional recommendation) 2
Surgery should be performed by experienced surgeons only after the patient has received several months of intensive chemotherapy 7

Never add a single drug to a failing regimen as this leads to acquired resistance to the new drug 7, 8
When initiating therapy for suspected drug-resistant TB, add at least two, preferably three, new drugs to which susceptibility can be inferred 7, 8
Treatment adherence is critical for successful outcomes; directly observed therapy (DOT) is strongly recommended 4, 9

Treatment for latent TB infection is recommended for contacts to patients with MDR-TB (conditional recommendation) 3
A 6-12 month regimen with a later-generation fluoroquinolone alone or with a second drug is suggested, based on drug susceptibility of the source case 3
Pyrazinamide should not be routinely used as the second drug due to increased toxicity and adverse events 3