title: A randomized evaluation of ethambutol for prevention of relapse and drug resistance during treatment of Mycobacterium avium complex bacteremia with clarithromycin-based combination therapy. California Collaborative Treatment Group.
abstract: 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 log10 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.
authors.affiliation: University of Southern California School of Medicine, Los Angeles, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Dubé
authors.forename: F R
authors.initials: FR
authors.lastname: Sattler
authors.forename: F J
authors.initials: FJ
authors.lastname: Torriani
authors.forename: D
authors.initials: D
authors.lastname: See
authors.forename: D V
authors.initials: DV
authors.lastname: Havlir
authors.forename: C A
authors.initials: CA
authors.lastname: Kemper
authors.forename: M G
authors.initials: MG
authors.lastname: Dezfuli
authors.forename: S A
authors.initials: SA
authors.lastname: Bozzette
authors.forename: A E
authors.initials: AE
authors.lastname: Bartok
authors.forename: J M
authors.initials: JM
authors.lastname: Leedom
authors.forename: J G
authors.initials: JG
authors.lastname: Tilles
authors.forename: J A
authors.initials: JA
authors.lastname: McCutchan
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000995:Antitubercular Agents / Q000008:administration & dosage*; D016470:Bacteremia / Q000188:drug therapy*; D017291:Clarithromycin / Q000008:administration & dosage* / Q000009:adverse effects; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy*; D011446:Prospective Studies; D012008:Recurrence
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D004977:Ethambutol; D017291:Clarithromycin