Chemotherapy of Tuberculosis

Abstract

The management of tuberculosis (TB) can be a challenging process that has implications both for the affected patient and public health. Effective anti-TB chemotherapy both cures and renders the patient noncontagious. Biological factors specific to M. tuberculosis necessitate the use of multiple drugs for prolonged durations to adequately eradicate infection. Recommended regimens address the complexities of eliminating organisms from diverse reservoirs while preventing the emergence of drug resistance. First-line anti-TB therapy for drug susceptible disease effectively cures almost all patients within 6-9 months. The loss of first-line agents, due to resistance or intolerance, necessitates lengthy treatment courses, frequently 12-18 months or longer. Due to the long treatment times and the implications of missed doses, directly-observed therapy (DOT) is considered the standard of care. Drugs used for the treatment of TB have serious potential toxicities that require close monitoring and prompt response. A strong public health infrastructure and robust social supports are important elements to assure successful treatment. These numerous factors compel public health entities to take a lead role in the management of TB, either through the direct management of TB treatment or by assuring the activities of partner organizations.

FIGURE 1

Management of drug-susceptible TB. ^aEMB may be discontinued if isolate is known to be susceptible to INH, RIF, and PZA. ^bDelayed culture conversion should prompt consideration of acquired drug resistance, noncompliance, and malabsorption. ^cAdditional duration of treatment may be considered in the following settings: delayed clinical or radiographic improvement, cavitary disease regardless of sputum conversion, extensive disease, active smoking, diabetes, HIV, > 10% below ideal body weight, or other immunocompromising conditions.

FIGURE 2

Management of hepatotoxicity. (Prompt referral to a specialist may be indicated if dysfunction is severe or patient does not improve promptly.) ^aIf cholestatic pattern, RIF likely etiology and rifabutin may be appropriate substitute after normalization of LFT’s. ^bIf patient has extensive disease, meningitis, HIV coinfection, or requires a prolonged period off first-line agents, prompt initiation of a nonhepatotoxic regimen such as EMB, a fluoroquinolone, cycloserine, and an aminoglycoside should be pursued. ^cReferal to a hepatologist or gastroenterologist may be indicated for delayed improvement or severe symptoms (i.e., intractable nausea and vomiting, elevated INR, lethargy, or coma). ^dRechallenge with PZA can be considered if hepatitis was not severe. ^eSee “Treatment Regimens”.