Multidrug-resistant tuberculosis: treatment is empirical, for want of robust trials

Tuberculosis is said to be multi-drug-resistant (MDR-TB) when the mycobacterial strain is resistant to both isoniazid and rifampicin in vitro, and "extensively multidrug-resistant" (XDR-TB) when the strain is also resistant to fluoroquinolones and to at least one aminoglycoside or capreomycin. Multidrug resistance greatly increases the lethality of tuberculosis. Patients with multidrug-resistant tuberculosis are usually treated for at least 20 months with a combination of five antibiotics. For want of better alternatives, extensively resistant disease is often treated with antibiotics that have both uncertain efficacy and major adverse effects. Antitubercular drug combinations have multiple adverse affects and many drug interactions. In practice, the choice of drugs is usually empirical, being based on bacteriological criteria and using antibiotics with uncertain efficacy but documented harms.