Treatment and prophylaxis of Mycobacterium avium complex

Abstract

The most common pathogens involved in disseminated bacterial infection in people with acquired immunodeficiency syndrome (AIDS) are organisms of the Mycobacterium avium-intracellulare complex (MAC). Azithromycin and clarithromycin, a new azalide and macrolide, respectively, are among the most potent monotherapies for MAC bacteraemia, although many bloodstream isolates demonstrate increased minimum inhibitory concentrations after 4 months of treatment. Current recommended prophylaxis, based on the results of two randomized, double-blind, prospective studies, is rifabutin 300 mg daily for people with AIDS with <100 CD4 lymphocytes/mm3. In the beige mouse model, we have shown that both azithromycin and clarithromycin prevent MAC bacteraemia following repetitive oral challenge. Clinical trials are now underway to confirm these effects in man; comparative treatments include placebo, rifabutin and an azalide/macrolide plus rifabutin. While combinations might be more effective and reduce the emergence of resistance, the spectre of cytochrome P-450 drug interactions necessitates careful study before combination prophylactic approaches are accepted. Such interactions are associated with rifabutin and some macrolides, although azithromycin may be less problematic in this respect as it appears to have little potential to interact with other antimicrobial agents.