Tuberculosis: Treatment

The two aims of tuberculosis treatment are to interrupt tuberculosis transmission by rendering patients noninfectious and to prevent morbidity and death by curing patients with tuberculosis. Chemotherapy for tuberculosis became possible with the discovery of streptomycin in the mid-1940s. Randomized clinical trials clearly indicated that the administration of streptomycin to patients with chronic tuberculosis reduced mortality rates and led to cure in the majority of cases. However, monotherapy with streptomycin was frequently associated with the development of resistance to this drug and the attendant failure of treatment. With the discovery of para-aminosalicylic acid (PAS) and isoniazid, it became axiomatic that cure of tuberculosis required the concomitant administration of at least two agents to which the organism was susceptible. Furthermore, early clinical trials demonstrated that a long period of treatment—i.e., 12–24 months—was required to prevent recurrence.

The introduction of rifampin in the early 1970s heralded the era of effective short-course chemotherapy, with a treatment duration of <12 months. The discovery that pyrazinamide, which was first used in the 1950s, augmented the potency of isoniazid/rifampin regimens led to the use of a 6-month course of this triple-drug regimen as standard therapy.