Drug-resistant tuberculosis (DR-TB) is an emerging global health threat as treatment involves complex multiple drug regimens, which are longer and more toxic than standard therapy and yet have worse outcomes. In the presence of resistance to one or more first-line drugs, an alternative regimen should be designed. A major problem is the almost complete lack of published evidence regarding the optimal drug combinations and duration of treatment for the different types of DR-TB. Current principles, some of which are based on expert opinion, are that at least three new anti-TB agents should be added to a failing regimen and four agents when multidrug resistance is suspected. All first-line oral anti-TB agents to which the Mycobacterium tuberculosis strains are susceptible should be used, plus one fluoroquinolone. In addition, one injectable anti-TB agent and one or more second-line oral anti-TB agents should be added to the regimen until the target number of drugs is reached. The duration of treatment depends on the type of drug resistance, the type and number of drugs used in the regimen, and the extent of the disease. All forms of DR-TB should receive daily, not intermittent, therapy and all doses should be directly observed. Because of the high rate of adverse drug effects, careful monitoring and appropriate management of these adverse reactions are important to achieve successful treatment. Supportive measures, such as adequate nutrition along with emotional and social supports, are an important part of the treatment. Careful consideration is required when dealing with pregnant or lactating women and HIV co-infected patients, as well as in treatment of extrapulmonary DR-TB.
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