Summary
In patients with AIDS, disseminated Mycobacterium avium-intracellulare complex (MAC) infection is a common bacterial infection and is associated with considerable morbidity and mortality.
In placebo-controlled studies, rifabutin, clarithromycin and azithromycin (administered as single agents) have been shown to prevent the development of MAC bacteraemia in patients with advanced HIV disease. Clarithromycin also conferred a survival benefit over placebo, but this was not initially observed with either rifabutin or azithromycin.
Subsequently, the efficacy of single agent therapy was compared with that of combination treatment as prophylaxis against the development of disseminated MAC. In the AIDS Clinical Trials Group (ACTG) 196/Community Programs for Clinical Research on AIDS (CPCRA) 009 study, clarithromycin monotherapy and clarithromycin and rifabutin combination therapy regimens were both more effective than rifabutin monotherapy in reducing the incidence of MAC bacteraemia. However, the combination regimen was generally not well tolerated. In the California Consortium Treatment Group (CCTG)/Multiple Opportunistic Prevention Prophylactic Strategy (MOPPS) study, azithromycin plus rifabutin was significantly more effective than either agent administered alone, and azithromycin was more effective than rifabutin. However, azithromycin (alone or in combination with rifabutin) caused frequent gastrointestinal adverse events. Emergence of resistance in those failing prophylaxis appeared to be higher with clarithromycin than with azithromycin or rifabutin. The use of the combination regimen of clarithromycin plus rifabutin did not reduce the selection of clarithromycin-resistant isolates.
Several issues need to be considered in the choice of MAC prophylaxis for the individual patient. On the basis of efficacy and potential drug interactions with protease inhibitors, clarithromycin or azithromycin is preferred to rifabutin. However, rifabutin is less likely to result in the emergence of resistance than the macrolides, and is likely to prevent tuberculosis, whereas azithromycin and clarithromycin will prevent some bacterial infections. Combination therapy for prophylaxis is not indicated in most situations.
Similar content being viewed by others
References
Horsburgh Jr CR. Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. N Engl J Med 1991; 324: 1332–83
Barradell LB, Plosker GL, McTavish D. Clarithromycin: a review of its pharmacological properties and therapeutic use in Mycobacterium avium-intracellulare complex infection in patients with acquired immune deficiency syndrome. Drugs 1993; 46(2): 289–312
Benson CA, Ellner JJ. Mycobacterium avium complex infection and AIDS: advances in theory and practice. Clin Infect Dis 1993: 17(1): 7–20
Nightingale SD, Cameron DW, Gordin FM, et al. Two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex infection in AIDS. N Engl J Med 1993; 329: 828–33
Moore RD, Chaisson RE. Survival analysis of two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex. AIDS 1995; 9: 1337–42
Pierce M, Crampton S, Henry D, et al. A randomised trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome. N Engl J Med 1996; 335: 384–91
Oldfield EC, Dickinson G, Chung R, et al. Once weekly azithromycin for the prevention of Mycobacterium avium complex (MAC) infection in AIDS patients [abstract no. 203]. 3rd Conference on Retroviruses and Opportunistic Infections: 1996 Jan 28–Feb 1: Washington: 90
Benson CA, Cohn DL, Williams P, et al. A phase III prospective, randomized, double-blind study of the safety and efficacy of clarithromycin (CLA) vs. rifabutin (RBT) vs. CLA + RBT for prevention of Mycobacterium avium complex disease in HIV+ patients with CD4+ counts ≤ 100 cells/μL [abstract no. 205]. 3rd Conference on Retroviruses and Opportunistic Infections: 1996 Jan 28–Feb 1: Washington: 91
Cohn DL, Benson CA, Williams P, et al. A prospective, randomized, double-blind, comparative study of the safety and efficacy of clarithromycin (CLA) vs rifabutin (RBT) vs the combination for the prevention of Mycobacterium avium complex (MAC) bacteremia or disseminated MAC disease (DMAC) in HIV-infected patients (pts) with CD4 counts ≤ 100 cells/mm3 [abstract no. WEB 421]. Xlth International Conference on AIDS: 1996 Jul 7–12: Vancouver: 27
Havlir DV, Dube MP, Sattler FR, et al. Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. N Engl J Med 1996; 335: 392–8
Shafran SD, Singer J, Zarowny DP, et al. A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS: rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. N Engl J Med 1996; 335: 377–83
DATRI 001 Study Group. Coadministration of clarithromycin alters the concentration-time profile of rifabutin [abstract A2]. 34th Interscience Conference on Antimicrobial Agents and Chemotherapy: 1994 Oct 4–7: Orlando
Carpenter CC, Fischl MA, Hammer SM, et al. Antiretroviral therapy for HIV infection in 1996: recommendations of an international panel. JAMA 1996; 276: 146–54
The Indinavir (MK 639) Pharmacokinetic Study Group. Indinavir (MK 639) drug interaction studies [abstract no. MOB 174]. XI International Conference on AIDS: 1996 Jul 7–12: Vancouver: 18-9
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cohn, D.L. Prevention Strategies for Mycobacterium avium-intracellulare Complex (MAC) Infection. Drugs 54 (Suppl 2), 8–15 (1997). https://doi.org/10.2165/00003495-199700542-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199700542-00004