Rifabutin: A New Rifamycin for the Prevention of Atypical Mycobacterial Infection

Abstract

Objective: To discuss the chemistry, mechanism of action, in vitro activity, pharmacology, clinical efficacy, and toxicity of rifabutin, a new rifamycin, in the prevention and treatment of disseminated mycobacterial infection in patients with AIDS. Data Sources: The English-language literature was searched from 1980 through October 1993 using MEDLINE, International Pharmaceutical Abstracts (IPA), Index Medicus, and bibliographic reviews of relevant textbooks and review articles. Study Selection: One published report of two identical randomized, prospective, double-blind trials of rifabutin to prevent disseminated mycobacteremia is available. Other literature reviewed included a clinical case series of patients treated with rifabutin for documented or presumed mycobacterial infection. Data Extraction: Clinical trial and case series were evaluated for study design, efficacy, and toxicity. Data Synthesis: In two trials, rifabutin has been shown to prolong the onset of mycobacteremia (caused by Mycobacterium avium-intracellulare or M. avium complex) in adult AIDS patients with CD4-lymphocyte counts <200 cells/mm3. The prolongation of time to bacteremia is significant compared with placebo as the CD4 count declines. However, overall survival is not prolonged by rifabutin prophylaxis in these patients. No blind, randomized studies are available evaluating the efficacy of rifabutin in treating documented mycobacteremia in AIDS patients, or in treating pulmonary infections caused by Mycobacterium tuberculosis. Conclusions: Rifabutin should be added to the prophylactic regimens of HIV-positive patients with CD4 counts <100 cells/mm3. Prophylactic treatment prolongs the period of time before dissemination of mycobacterial infection occurs (bacteremia), with associated delays in onset of fever and fatigue, decline in performance score, and hospitalization. Rifabutin is usually well tolerated in patients given 300 mg/d. Rifabutin is a weaker enzyme inducer than rifampin, but drug interactions with rifabutin should be monitored under circumstances of concomitant therapy with anticoagulants or anticonvulsants.