Mycobacterium avium complex infection. Pharmacokinetic and pharmacodynamic considerations that may improve clinical outcomes.

Mycobacterium avium complex (MAC) is an infrequent pulmonary pathogen in immunocompetent hosts. In patients with AIDS, MAC causes disseminated infection (DMAC) in up to 50% of those with CD4+ counts less than 100 cells/mm3. A significant portion of the total body burden of MAC is found inside macrophages, and the distribution of organisms has implications for drug therapy. Clarithromycin, azithromycin, and rifabutin all appear to enter these cells well; rifampicin (rifampin), ethambutol, ciprofloxacin, and other agents also appear to enter these cells. MAC susceptibility is probably best tested using the radiometric method (BACTEC). Susceptibility break-points have been proposed for the various anti-MAC agents; however, solid clinical correlations have been achieved only for clarithromycin. Further research is required to establish break-points for the other agents. Based on current data, azithromycin and clarithromycin appear to be key drugs in the treatment of MAC, while rifabutin has been used more often than rifampicin in studies involving patients with AIDS. Among the drugs traditionally used for M. tuberculosis (TB), ethambutol, rifampicin and streptomycin are perhaps the most useful for MAC. Amikacin and clofazimine may also be useful. The limited data available on AIDS patients with MAC, plus additional data from AIDS patients with TB, suggest that malabsorption of the oral antimycobacterial drugs is common. Some drugs (rifampicin and ethambutol) appear to be particularly affected. Because most of the studies of DMAC have not evaluated the pharmacokinetics of the drugs, questions of drug efficacy cannot be separated from questions of biovailability. This significant oversight in study design should be eliminated from future investigations. Patient-specific susceptibility data combined with therapeutic drug monitoring and dosage individualisation is one way to identify problems with drug therapy and to overcome them. Because many of the drugs used in patients with AIDS affect the metabolism of concurrently used drugs, therapeutic drug monitoring is a valuable asset for untangling multiple drug interactions. Since drug therapy is the only aspect of a mycobacterial infection within our control, the better we control the drug therapy, the better our patients should do.