Rationale for the Use of Azithromycin as Mycobacterium avium Chemoprophylaxis

Abstract

The development of disseminated Mycobacterium avium complex (MAC) disease in HIV-infected patients is associated with significant morbidity and mortality. Azithromycin is an azalide antibiotic of the macrolide family that has been shown to accumulate within macrophages at levels exceeding the 90% minimum inhibitory concentration (MIC 90) of Mycobacterium avium. The dibasic nucleus of the molecule is responsible for its prolonged retention at elevated levels within the lysosome. Azithromycin is not significantly metabolized through the cytochrome P-450 enzyme system and consequently is not associated with significant drug interactions. Numerous animal models of MAC infection have provided preclinical support for activity in vivo. Based on these data, two randomized, comparative, double-blind studies were performed to assess the activity of azithromycin, given as 1,200 mg once weekly, in human immunodeficiency virus (HIV)-infected patients with CD4 counts <100 cells/mm 3. The results of these trials revealed a significant protective effect of azithromycin over placebo and efficacy at least as good as rifabutin. Resistance to macrolides in the breakthrough MAC isolates was uncommon (0–11%). The strength of these efficacy findings was associated with a low rate of discontinuation for side effects over the course of 1 year of therapy (8–14%). The use of azithromycin is a safe, effective, and convenient option for prophylaxis of disseminated MAC in HIV-infected patients.