Prevention strategies for Mycobacterium avium-intracellulare complex (MAC) infection - A review of recent studies in patients with AIDS

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 mon 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 clarithromvcin-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 clarithrmycin will prevent some bacterial infections. Combination therapy for prophylaxis is not indicated in most situations.