Activity of clarithromycin against Mycobacterium avium infection in patients with the acquired immune deficiency syndrome: A controlled clinical trial

Disseminated Mycobacterium avium infection is common in patients with acquired immune deficiency syndrome (AIDS), but no drug studies have been reported establishing antimicrobial activity against this organism in a controlled, randomized trial. Clarithromycin, a new macrolide, has activity against M. avium in vitro and in animals, but it has not been studied in humans. In this randomized, double-blind, placebo-controlled trial, we measured the ability of clarithromycin to reduce M. avium bacteremia in patients with AIDS and disseminated infection. Of 23 patients initially enrolled, 15 men with late-stage AIDS qualified for the study. One group received clarithromycin alone for 6 wk, then placebo plus rifampin, isoniazid, ethambutol, and clofazimine for 6 wk. The other group received placebo alone, then clarithromycin plus the other four drugs. Colony-forming units (CFU) of M. avium per milliliter of blood were determined by quantitative cultures taken at baseline and every 2 wk thereafter. Minimum inhibitory concentration of clarithromycin for 90% of the strains isolated from patients at baseline, as measured on 7H11 agar at pH 6.6, was 8 μg/ml. Eight eligible patients with initial positive cultures who were initially receiving clarithromycin alone had marked declines in blood M. avium CFU; in six cases, CFU decreased to zero. When seven patients were switched to placebo plus the other four drugs, CFU rose in four patients and remained undetectable in three. The five eligible patients initially treated with placebo had progressive CFU increases; when three were switched to clarithromycin plus the four drugs, their CFU declined. We conclude that clarithromycin has consistent activity against M. avium and may benefit patients with AIDS and disseminated M. avium infection.