Disseminated Infection with Mycobacterium avium Complex

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 <50 cells/uL (AI) (38). 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, 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 confer protection against respiratory bacterial infections (BII). If clarithromycin or azithromycin cannot be tolerated, rifabutin is an alternative prophylactic agent for MAC disease (BI) (38, 39, 41). 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 non-nucleoside reverse transcriptase inhibitors is warranted (see Drug Interaction Note). Before prophylaxis is initiated, disseminated MAC disease should be ruled out by clinical assessment, which may 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, the latter condition should also be excluded before rifabutin is used for prophylaxis.

(3) Although the detection of MAC organisms in the respiratory or gastrointestinal tract may be predictive of 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 at this time (DIII).

Discontinuation of Primary Prophylaxis
(4) Information from one observational study suggested a low rate of disseminated infection with MAC among persons who responded to HAART with an increase in CD4+ T-lymphocyte count from < 50 cells/uL to > 100 cells/uL (31). While the optimal criteria for discontinuation of MAC prophylaxis remain to be defined, it is reasonable to consider discontinuing prophylaxis in patients with a sustained CD4+ T-lymphocyte count of > 100 cells/uL (e.g. > 3-6 months) and sustained suppression of HIV plasma RNA (CIII).

Restarting Primary Prophylaxis
(5) There are no data on which to base recommendations for reinstitution of prophylaxis. Pending the availability of such data, a reasonable approach would be to utilize the criteria for initiation of prophylaxis described above (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) (38). Unless there is good clinical or laboratory evidence of macrolide resistance, the use of a macrolide (clarithromycin or, alternatively, azithromycin) is recommended in combination with ethambutol (AII) with or without rifabutin (CI). Treatment of MAC disease with clarithromycin in a dose of 1,000 mg twice a day is associated with a higher mortality rate than observed with clarithromycin administered at 500 mg twice a day; thus, the higher dose should not be used (EI) (42, 43). Clofazimine has been associated with a worse clinical outcome in the treatment of MAC disease and should not be used (DII) (43).

Discontinuation of Secondary Prophylaxis (chronic maintenance therapy)
(7) Although patients receiving chronic maintenance therapy for MAC may be at low risk for recurrence of MAC when their CD4+ T-lymphocyte counts increase to > 100 cells/uL following 6-12 months of HAART, the numbers of patients who have been evaluated are sufficient to warrant a recommendation at this time to discontinue maintenance therapy in such patients.

Notes

Drug Interaction Note
(8) Rifabutin should not be administered with certain protease inhibitors or non-nucleoside reverse transcriptase inhibitors (see Drug Interaction Note in section on Tuberculosis). Although protease inhibitors may also increase clarithromycin levels, no recommendation for dose adjustment of either clarithromycin or protease inhibitors can be made based on existing data.

Pediatric Note
(9) HIV-infected children aged <13 years who have advanced immunosuppression may also develop disseminated MAC infections, and prophylaxis should be offered to high-risk children according to the following CD4+ T-lymphocyte thresholds: children aged >6 years, <:50 cells/uL; children aged 2-6 years, <75 cells/uL; children aged 1-2 years, <500 cells/uL; and children aged <12 months, <750 cells/uL (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 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 be studied.

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

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