Treatment Regimens for Tuberculosis Based on Drug Susceptibility Test Results

Initial Treatment Approach

The Centers for Disease Control and Prevention recommends that all patients with TB should have drug susceptibility testing performed on their first isolate to guide therapeutic decisions 1, 3
The initial treatment regimen should consist of a four-drug regimen of isoniazid, rifampin, pyrazinamide, and ethambutol (or streptomycin) for the first 2 months (intensive phase) 2, 4
This initial four-drug regimen is highly effective even for isoniazid-resistant organisms when adherence is assured 5
Drug susceptibility testing should be performed on additional isolates if cultures fail to convert to negative within 3 months or if there is clinical evidence of treatment failure 3

When DST confirms susceptibility to isoniazid and rifampin, the American Thoracic Society recommends continuing with isoniazid and rifampin for a total of 6 months, with pyrazinamide only needed during the first 2 months 3, 4
Daily dosing is strongly recommended for optimal efficacy 4

For isoniazid-resistant but rifampin-susceptible TB, the American Journal of Respiratory and Critical Care Medicine suggests continuing rifampin and ethambutol for a minimum of 12 months, and pyrazinamide may be included in the regimen when the M. tuberculosis isolate has not been found resistant to it 6

For MDR-TB (resistant to at least isoniazid and rifampin), treatment should include at least five drugs in the intensive phase and four drugs in the continuation phase, a later-generation fluoroquinolone, bedaquiline, and consideration of linezolid, clofazimine, and cycloserine, with a treatment duration of 15-21 months after culture conversion 6

For pre-XDR and XDR-TB, the American Journal of Respiratory and Critical Care Medicine recommends extending treatment to 15-24 months after culture conversion, and including at least three drugs to which the organism is likely to be susceptible 6, 7

The Centers for Disease Control and Prevention recommends that HIV-infected patients with TB should be treated for a total of 9 months and for at least 6 months after sputum conversion, and rifabutin should be substituted for rifampin with appropriate dose adjustments when patients are receiving protease inhibitors or NNRTIs 8, 4

The American Thoracic Society recommends that regimens for extrapulmonary TB follow the same principles as pulmonary TB, and consider extending treatment to 9 months for disseminated disease, miliary disease, bone/joint TB, or tuberculous lymphadenitis 8

The American Journal of Respiratory and Critical Care Medicine recommends monitoring response to therapy with follow-up sputum smear microscopy and culture, and performing additional drug susceptibility testing if cultures remain positive after 3 months of treatment 4, 3

The American Journal of Respiratory and Critical Care Medicine advises never adding a single drug to a failing regimen as this leads to acquired resistance, and avoiding delays in adjusting treatment after receiving DST results 7, 6
The American Thoracic Society recommends monitoring for drug interactions, especially with rifampin which affects many medications including oral contraceptives, anticoagulants, and antiretroviral drugs, and watching for hepatotoxicity, particularly during the first 2 months of treatment 4