Disseminated infection with Mycobacterium Avium Complex (MAC)
UPHS/IDSA Guidelines		 
Prevention of Exposure
1. Organisms of the M. avium complex (MAC) are common in environmental sources such as food and water. Current information does not support specific recommendations regarding avoidance of exposure.

Prevention of Disease
Initiation of Primary Prophylaxis

2. Adults and adolescents who have HIV infection should receive chemoprophylaxis against disseminated MAC disease if they have a CD4+ T-lymphocyte count of less than 50 cells/無 (AI) (4). Clarithromycin (39,40) or azithromycin (41) are the preferred prophylactic agents (AI). The combination of clarithromycin and rifabutin is no more effective than clarithromycin alone for chemoprophylaxis and is associated with a higher rate of adverse effects than either drug alone; this combination should not be used (EI) (39). The combination of azithromycin with rifabutin is more effective than azithromycin alone; however, the additional cost, increased occurrence of adverse effects, potential for drug interactions, and absence of a difference in survival when compared with azithromycin alone do not warrant a routine recommendation for this regimen (CI) (41). In addition to their preventive activity for MAC disease, clarithromycin and azithromycin each confer protection against respiratory bacterial infections (BII). If clarithromycin or azithromycin cannot be tolerated, rifabutin is an alternative prophylactic agent for MAC disease (BI) (39,41,42). Tolerance, cost, and drug interactions are among the issues that should be considered in decisions regarding the choice of prophylactic agents for MAC disease. Particular attention to interactions with antiretroviral protease inhibitors and nonnucleoside reverse transcriptase inhibitors is warranted (see Special Considerations/Drug Interactions, page 15). Before prophylaxis is initiated, disseminated MAC disease should be ruled out by clinical assessment, which might include obtaining a blood culture for MAC if warranted. Because treatment with rifabutin could result in the development of resistance to rifampin in persons who have active tuberculosis, active tuberculosis should also be excluded before rifabutin is used for prophylaxis.

3. Although the detection of MAC organisms in the respiratory or gastrointestinal tract might predict the development of disseminated MAC infection, no data are available on the efficacy of prophylaxis with clarithromycin, azithromycin, rifabutin, or other drugs in patients with MAC organisms at these sites and a negative blood culture. Therefore, routine screening of respiratory or gastrointestinal specimens for MAC cannot be recommended (DIII).

Discontinuation of Primary Prophylaxis
4. Information from observational studies suggested a low rate of disseminated infection with MAC among persons who responded to HAART with an increase in CD4+ T-lymphocyte count from less than 50 cells/無 to greater than 100 cells/無 (32,43). Although the optimal criteria for discontinuing MAC prophylaxis remain to be defined, a reasonable option would be to consider discontinuing prophylaxis in patients with a CD4+ T-lymphocyte count of greater than 100 cells/無 for a sustained period (e.g., greater than 3-6 months) and sustained suppression of HIV plasma RNA for a similar period (CII).

Restarting Primary Prophylaxis
5. No data are available on which to base recommendations for reinstituting prophylaxis. Pending the availability of such data, a reasonable approach would be to use the criteria for initiating prophylaxis described on page 14 (CIII).

Prevention of Recurrence
6. Patients who have been treated for disseminated MAC disease should continue to receive full therapeutic doses of antimycobacterial agents for life (i.e., secondary prophylaxis or chronic maintenance therapy) (AII) (42). Unless good clinical or laboratory evidence of macrolide resistance exists, the use of a macrolide (clarithromycin or, alternatively, azithromycin) is recommended in combination with ethambutol (AII) with or without rifabutin (CI) (44,45). Treatment of MAC disease with clarithromycin in a dose of 1,000 mg twice a day is associated with a higher mortality rate than has been observed with clarithromycin administered at 500 mg twice a day; thus, the higher dose should not be used (EI) (46,47). Clofazimine has been associated with an adverse clinical outcome in the treatment of MAC disease and should not be used (DII) (47,48).

Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy)
7. Although patients receiving chronic maintenance therapy for MAC might be at low risk for recurrence of MAC when their CD4+ T-lymphocyte counts increase to greater than 100 cells/無 following 6-12 months of HAART, the numbers of patients who have been evaluated are insufficient to warrant a recommendation to discontinue maintenance therapy in such patients.

Special Considerations

Drug Interaction Note
8. Rifabutin should not be administered with certain protease inhibitors or nonnucleoside reverse transcriptase inhibitors (see Special Considerations/Drug Interactions in Tuberculosis section, page 13). Although protease inhibitors might also increase clarithromycin levels, no recommendation to adjust the dose of either clarithromycin or protease inhibitors can be made on the basis of existing data.

Children
9. HIV-infected children aged less than 13 years who have advanced immunosuppression also can develop disseminated MAC infections, and prophylaxis should be offered to high-risk children according to the following CD4+ T-lymphocyte thresholds: children aged greater than or equal to 6 years, less than 50 cells/無; children aged 2-6 years, less than 75 cells/無; children aged 1-2 years, less than 500 cells/無; and children aged less than 12 months, less than 750 cells/無 (AII). For the same reasons that clarithromycin and azithromycin are the preferred prophylactic agents for adults, they should also be considered for children (AII); oral suspensions of both agents are commercially available in the United States. No liquid formulation of rifabutin suitable for pediatric use is commercially available in the United States. The safety of discontinuing MAC prophylaxis in children whose CD4+ T-lymphocyte counts have increased in response to HAART has not been studied.

Pregnant Women
10. Chemoprophylaxis for MAC disease should be administered to pregnant women as is done for other adults and adolescents (AIII). However, because of general concerns about administering drugs during the first trimester of pregnancy, some providers may choose to withhold prophylaxis during the first trimester. Animal studies and anecdotal evidence of safety in humans suggest that of the available agents, azithromycin is the drug of choice (BIII) (49). Experience with rifabutin is limited. Clarithromycin has been demonstrated to be a teratogen in animals and should be used with caution during pregnancy (50). For secondary prophylaxis (chronic maintenance therapy), azithromycin plus ethambutol are the preferred drugs (BIII).

[arrow]PHS index[arrow]Network index


The Network
format © copyright 2000 The Network

HOME