A Randomized, Placebo-Controlled Study of Rifabutin Added to a Regimen of Clarithromycin and Ethambutol for Treatment of Disseminated Infection with Mycobacterium avium Complex

• Published in: Clinical infectious diseases Vol. 28; no. 5; pp. 1080 - 1085
• Main Authors: Gordin, Fred M., Sullam, Paul M., Shafran, Stephen D., Cohn, David L., Wynne, Beverley, Paxton, Linda, Perry, Kim, Horsburgh, C. R.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.05.1999; University of Chicago Press
• Subjects: Adolescent; Adult; AIDS; AIDS-Related Opportunistic Infections - drug therapy; AIDS/HIV; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - therapeutic use; Bacteremia; Bacterial diseases; Biological and medical sciences; Blood; Child; Clarithromycin - therapeutic use; Clinical Articles; Drug Resistance, Microbial; Drug Therapy, Combination - therapeutic use; Ethambutol - therapeutic use; Female; Fever; Human bacterial diseases; Humans; Infections; Infectious diseases; Male; Medical sciences; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection - drug therapy; Pharmacology. Drug treatments; Placebos; Prospective Studies; Relapse; Rifabutin - therapeutic use; Survival Analysis; Sweat; Symptoms; Tuberculosis and atypical mycobacterial infections; Human; Opportunistic infection; Drug combination; Clarithromycin; Prognosis; Treatment efficiency; Mycobacterium avium; Mycobacterial infection; Macrolide; Infection; Rifabutin; Antibiotic; Chemotherapy; Treatment; Mycobacteriales; Bacteriosis; Mycobacteriaceae; Bacteria; Ethambutol; Actinomycetes; Disseminated; Antibacterial agent
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/514748

Current guidelines suggest that disseminated Mycobacterium avium complex (MAC) infection be treated with a macrolide plus ethambutol or rifabutin or both. From 1993 to 1996, 198 AIDS patients with MAC bacteremia participated in a prospective, placebo-controlled trial of clarithromycin (500 mg b.i.d.) plus ethambutol (1,200 mg/d), with or without rifabutin (300 mg/d). At 16 weeks, 63% of patients in the rifabutin group and 61% in the placebo group (P = .81) had responded bacteriologically. Changes in clinical symptoms and time to survival were similar in both groups. Development of clarithromycin resistance during therapy was similar in the two groups; of patients who had a bacteriologic response, however, only 1 of 44 (2%) receiving rifabutin developed clarithromycin resistance, vs. 6 of 42 (14%) in the placebo group (P = .055). Thus, rifabutin had no impact on bacteriologic response or survival but may protect against development of clarithromycin resistance in those who respond to therapy.