Rifabutin prophylaxis for Mycobacterium avium complex infection in patients with AIDS

Rifabutin, a macrophage-penetrating lipophilic rifamycin, has a long half-life and activity in vitro against Mycobacterium avium complex (MAC). Preliminary studies of patients with AIDS and those with AIDS-related complex defined dose-limiting toxic effects (arthralgia/arthritis and uveitis) and suggested that rifabutin alone might reduce the incidence of MAC infections. Two double-blind, randomized, placebo-controlled trials involving 1,100 subjects confirmed the safety and efficacy of low doses of rifabutin; this therapy halved the rate of MAC bacteremia and significantly reduced symptoms associated with disseminated MAC infections. Subsequent experience with rifabutin as prophylaxis for and treatment of MAC infections has generally supported its safety profile. Emergence of drug-resistant MAC causing infection in patients receiving rifabutin therapy has not been reported. Interactions with azoles and macrolides increase blood levels of rifabutin and have led to the development of uveitis in certain patients. Studies of the cost-effectiveness of rifabutin prophylaxis for MAC infection suggest that it is comparable with other preventive interventions employed in clinical practice.