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, more than 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, where the HIV epidemic rages. Effective drug regimens are not all that is 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.
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 with the regimen 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 given daily or twice weekly for 9 months), rifampin (daily for 4 months), or isoniazid plus rifapentine (weekly for 3 months) (Table 77-1).
TABLE 77-1REGIMENS FOR THE TREATMENT OF LATENT TUBERCULOSIS INFECTION IN ADULTS ||Download (.pdf) TABLE 77-1 REGIMENS FOR THE TREATMENT OF LATENT TUBERCULOSIS INFECTION IN ADULTS
|REGIMEN ||SCHEDULE ||DURATION ||COMMENTS |
|Isoniazid || |
300 mg/d (5 mg/kg)
Alternative: 900 mg twice weekly (15 mg/kg)
|9 months (6 months acceptable) || |
Supplement with pyridoxine (25–50 mg daily).
Twice-weekly regimens require directly observed therapy.
|Rifampin ||600 mg/d (10 mg/kg) ||4 months ||Broader efficacy studies are needed. |
|Isoniazid plus rifapentine ||900 mg (15 mg/kg) weekly + 900 mg weekly ||3 months || |
Directly observed therapy is recommended for once-weekly treatment.
This regimen may be supplemented with pyridoxine (25–50 mg/d).
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 (...