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Chapter 7 : Chemotherapy of Tuberculosis
Category: Clinical Microbiology; Bacterial Pathogenesis
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This chapter reviews the underlying principles of tuberculosis (TB) chemotherapy, medical management, and current treatment recommendations. TB is caused by members of the Mycobacterium tuberculosis complex, with M. tuberculosis being responsible for the vast majority of disease. Early in the history of anti-TB chemotherapy, the highly effective agent streptomycin (SM) was applied as monotherapy. Current first-line regimens consist of three or four agents that, in concert, can eradicate organisms within all compartments and prevent the development of drug resistance. Isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), ethambutol (EMB), and SM are the five standard first-line agents. Elevated transaminases, clinical hepatitis, and peripheral neuropathy are among the most common adverse events seen with INH. M. tuberculosis strains resistant to SM may be susceptible to other aminoglycosides, but the susceptibility to each agent must be confirmed by resistance testing. The drugs used in the standard treatment of pulmonary TB are recommended for all extrapulmonary TB. In patients with renal dysfunction, PZA and EMB dosing should be adjusted. Serum levels of drugs should be obtained to ensure adequate treatment if any question of adequacy exists. Patients may require intramuscular and intravenous treatment regimens until oral absorption can be ensured. Diagnosis of TB is often based on smear microscopy without culture. Fixed- dose combinations of anti-TB agents are recommended to prevent the use of inadequate regimens and monotherapy.
Management of drug-susceptible pulmonary TB. *, EMB may be discontinued if susceptibility to other first-line agents is ensured; **, rifapentene may be an appropriate substitution in HIV-negative patients with noncavitary disease and sputum smear conversion during the initial phase; ***, additional duration of treatment may be considered for delayed clinical or radiographic improvement; ****, delayed culture conversion should prompt consideration of acquired drug resistance, noncompliance, and malabsorption.
Reinstitution of interrupted or incomplete anti-TB treatment. © 2008 by The City of New York, Department of Health and Mental Hygiene. All rights reserved. (Adapted from Tuberculosis Clinical Policies and Protocols, 4th ed. Bureau of Tuberculosis Control, New York City Department of Health and Mental Hygiene, New York, NY, 2008) ( 3 ).
Management of hepatotoxicity. *, if there is a cholestatic pattern, RIF is the likely etiology and RFB may be an appropriate substitute after normalization of liver function tests (LFTs); **, if the patient has extensive disease, meningitis or HIV coinfection or requires a prolonged period off first-line agents, prompt initiation of a nonhepatotoxic regimen such as EMB, SM, and a fluoroquinolone should be pursued; ***, rechallenge with PZA can be considered if hepatitis was not severe.
Dosing of first-line TB drugs a
Weight-based dosing for PZA and EMB
Alternative treatment regimens in patients intolerant or resistant to INH, RIF, or PZA
Dosing with renal dysfunction a
Preferred first-line treatment regimens a