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Agents used for the treatment of mycobacterial infections, including tuberculosis (TB), leprosy (Hansen's disease), and infections due to nontuberculous mycobacteria (NTM), are administered in multiple-drug regimens for prolonged courses. Currently, more than 150 species of mycobacteria have been identified, the majority of which do not cause disease in humans. While the incidence of disease caused by M. tuberculosis has been declining in the United States, TB remains a leading cause of morbidity and mortality in developing countries—particularly in sub-Saharan Africa, where the HIVepidemic rages. Not only effective drug regimens are needed; without a well-organized infrastructure for diagnosis and treatment of TB, therapeutic and control efforts are severely hampered. Infections with NTM have gained in clinical prominence in the United States and other developed countries. These largely environmental organisms often establish infection in immunocompromised patients or in persons with structural lung disease.

General Principles

The earliest recorded human case of TB dates back 9000 years. Early treatment modalities, such as bloodletting, were replaced by sanatorium regimens in the late 19th century. The discovery of streptomycin in 1943 launched the era of antibiotic treatment for TB. Over subsequent decades, the discovery of additional agents and the use of multiple-drug regimens allowed progressive shortening of the treatment course from years to as little as 6 months with the regimen for drug-susceptible TB. Latent TB infection (LTBI) and active TB disease are diagnosed by history, physical examination, tuberculin skin test, interferon γ release assay, radiographic imaging, and/or mycobacterial cultures. LTBI is treated with either isoniazid (9 months) or rifampin (4 months) (Table 168-1).

Table 168-1 Regimens for the Treatment of Latent Tuberculosis Infection (LTBI) in Adults

For active or suspected TB disease, clinical factors, including HIV co-infection, symptom duration, radiographic appearance, and public health concerns about TB transmission, drive diagnostic testing and treatment initiation. Multiple-drug regimens are used for the treatment of TB disease (Table 168-2). Initially, an intensive phase consisting of four drugs—isoniazid, rifampin, pyrazinamide, and ethambutol given for 2 months—is followed by a continuation phase of isoniazid and rifampin for 4 months, for a total treatment duration of 6 months. The continuation phase is extended to 7 months (for a total treatment duration of 9 months) if the 2-month course of pyrazinamide is not completed or, for patients with cavitary pulmonary TB, ...

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