Randomized evaluation of ethambutol for prevention of relapse and drug resistance during treatment of Mycobacterium avium complex bacteremia with clarithromycin-based combination therapy

Patients with AIDS and Mycobacterium avium complex (MAC) bacteremia are at high risk for relapse and emergence of resistant isolates during monotherapy with clarithromycin, Ninety-five AIDS patients with MAC bacteremia received clarithromycin plus clofazimine, with or without ethambutol, in a prospective, multicenter, randomized open-label trial, Of 80 patients with positive baseline cultures, sterilization or a 2 log(10) reduction in colony-forming units of MAC in two consecutive blood cultures occurred in 69% of both groups. There were nine relapses in the two-drug arm and three in the three-drug arm, Kaplan-Meier estimates of risk of relapse at 36 weeks were 68% and 12%, respectively (P = .004), All relapse isolates were resistant to clarithromycin, Median time to clarithromycin resistance was 16 weeks with two drugs and 40 weeks with three drugs (P = .004), Ethambutol reduced relapses and emergence of clarithromycin resistance and should be considered an essential component of clarithromycin-based therapies for MAC bacteremia.