Agents used for the treatment of mycobacterial infections, including tuberculosis (TB), leprosy, and infections due to nontuberculous mycobacteria (NTM), are administered in multiple-drug regimens for prolonged courses. Currently, >160 species of mycobacteria have been identified, the majority of which do not cause disease in humans. While the incidence of disease caused by Mycobacterium 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 and Asia, where the HIV epidemic 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 (Chaps. 460 and 462). 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.
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 nineteenth 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 for drug-susceptible TB. Latent TB infection (LTBI) and active TB disease are diagnosed by history, physical examination, radiographic imaging, tuberculin skin test, interferon γ release assays, acid-fast staining, mycobacterial cultures, and/or new molecular diagnostics. LTBI is treated with isoniazid (optimally daily or weekly for 9 months), rifampin (daily for 4 months), isoniazid plus rifampin (daily for 3 months), or isoniazid plus rifapentine (weekly for 3 months) (Table 176-1).
TABLE 176-1Regimens for the Treatment of Latent Tuberculosis Infection in Adults ||Download (.pdf) TABLE 176-1 Regimens for the Treatment of Latent Tuberculosis Infection in Adults
|Regimen ||Schedule ||Duration ||Comments |
|Isoniazid ||300 mg/d (5 mg/kg) ||9 months (6 months acceptable) ||Supplement with pyridoxine (25–50 mg daily). |
|Alternative: 900 mg twice weekly (15 mg/kg) ||Twice-weekly regimens require directly observed therapy. |
|Rifampin ||600 mg/d (10 mg/kg) ||4 months ||Broader efficacy studies are needed. |
|Isoniazid plus rifampin ||300 mg/d (5 mg/kg) plus 600 mg/d (10 mg/kg) ||3 months ||Broader efficacy studies are needed. |
|Isoniazid plus rifapentine ||900 mg (15 mg/kg) weekly plus 900 mg (for weight >50 kg) weekly ||3 months ||Directly observed therapy is recommended for once-weekly treatment. This regimen may be supplemented with pyridoxine (25–50 mg/d). |