Disseminated Infection with Mycobacterium avium Complex
Prevention of Exposure
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
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/µL. Clarithromycin or azithromycin
are the preferred prophylactic agents. The combination of clarithromycin
and rifabutin is no more effective than clarithromycin alone for chemoprophylaxis
and is associated with a higher rate of ad-verse effects than either drug
alone; this combination should not be used. 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. In addition to their preventive activity
for MAC disease, clarithromycin and azithromycin confer protection against
respiratory bacterial infections. If clarithromycin or azithromycin
cannot be tolerated, rifabutin is an alternative prophylactic agent for MAC
disease. 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. 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
of antiretroviral protease inhibitors with rifabutin and, to a lesser extent,
clarithromycin, is warranted (see Drug Interaction Note).
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.
Prevention of Recurrence
Notes:
Pediatric Note
Note Regarding Pregnancy
Patients who are treated for disseminated MAC disease should continue
to be administered full therapeutic doses of antimycobacterial agents for
life. The choice of the drug regimen should be made in consultation
with an expert. Unless there is good clinical or laboratory evidence of macrolide
resistance, the use of a macrolide (clarithromycin or azithromycin) is
recommended in combination with at least one other drug (i.e., ethambutol
or rifabutin). Treatment of MAC disease with clarithromycin in
a dose of 1,000 mg twice a day is associated with decreased survival compared
with clarithromycin administered 500 mg twice a day; thus, the higher dose
should not be used. Clofazimine has been demonstrated not to be effective
in the treatment of MAC disease and should not be used.
Drug Interaction Note
Patients concurrently being administered protease inhibitor antiretroviral
therapy generally should not be administered rifabutin. However, if
co-administration of rifabutin and a protease inhibitor is necessary, indinavir
and nelfinavir are the preferred protease inhibitors, and the dose of rifabutin
should be reduced by 50% with either of these drugs. 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.
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+ thresholds: children
aged >6 years, <50 cells/µL; children aged 26 years,
<75 cells/µL; children aged 12 years, <500 cells/µL;
and children aged <12 months, <750 cells/µL. For the same
reasons that clarithromycin and azithromycin are the preferred prophylactic
agents for adults, they should also be considered for children; oral
suspensions of both are commercially available in the United States. A liquid
formulation of rifabutin suitable for pediatric use is under development
but currently is not commercially available in the United States.
Chemoprophylaxis for MAC disease should be administered to pregnant
women as well as to other adults and adolescents. 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 avail-able agents, the safety profile in animal studies
and anecdotal safety in humans suggest that azithromycin is the drug of choice. Experience with rifabutin is limited. Clarithromycin has been
demonstrated to be a teratogen in animals and should be used with caution
during pregnancy.
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