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6–62 | Clinical Manual for Management of the HIV-Infected Adult/2006
P: Plan
Diagnostic Evaluation
A definitive diagnosis requires isolation of MAC
from the blood or other normally sterile body fluids
or tissues (M avium cultured from sputum, bronchial
washing, or stool may represent colonization rather than
infection). Send blood for acid-fast bacilli (AFB) culture
(2-3 samples drawn at different times will increase
sensitivity).
Because MAC may take weeks to grow in culture,
ancillary studies should be performed. These are not
specific, but may be helpful in reaching a presumptive
diagnosis:
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Complete blood count (CBC) for anemia,
lymphopenia, thrombocytopenia
Serum alkaline phosphatase (often elevated in
DMAC)
Computed tomography (CT) scan of the chest
and abdomen (intra-abdominal and mediastinal
lymphadenopathy or hepatosplenomegaly are often
present)
If blood cultures are negative and MAC is suspected,
consider biopsy of the lymph nodes, bone marrow,
liver, or bowel (via endoscopy) to detect DMAC by
microscopic examination for AFB and culture. If
the evidence suggests pulmonary MAC, consider
bronchoscopy and bronchoalveolar lavage.
Perform additional studies as indicated to rule out other
causes of the patient's symptoms, including bacterial
blood cultures, sputum for M tuberculosis, Bartonella
studies, lymph node cytology for lymphoma, and stool
cultures.
Treatment
Because antimicrobial resistance develops quickly
with single-drug therapy, multidrug regimens must be
administered for DMAC.
The U.S. Centers for Disease Control and prevention
recommends the following 2-drug regimens:
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Clarithromycin 500 mg twice daily + ethambutol 15
mg/kg once daily,
Azithromycin 500-600 mg once daily + ethambutol
15 mg/kg once daily
Some experts recommend including a third agent
for more advanced disease or for patients not taking
effective ART. The addition of rifabutin (300 mg daily)
has been associated with increased mycobacterial
clearance, but no survival benefit. A fluoroquinolone
(eg, ciprofloxacin, levofloxacin) or amikacin may be used
instead of rifabutin as a third agent, or in addition to
rifabutin as a fourth agent; however, studies have not
confirmed the clinical benefit of these medications.
Because immune reconstitution is essential for
controlling MAC, all patients not already taking
ART should begin ART, if possible. Patients taking
suboptimal ART should be evaluated for enhancement
of their regimen. The optimal timing of ART initiation
in relation to MAC treatment is unclear. Because
immune reconstitution from effective ART may cause
a paradoxical inflammatory response if started during
active DMAC infection, some experts recommend
treating DMAC for about a month before adding
antiretroviral (ARV) medications (see chapter Immune
Reconstitution Syndrome). This strategy also helps
to avoid or forestall interactions between DMAC
and ARV drugs and the additive toxicities of these
medications.
Clarithromycin is often considered the macrolide of
choice for use in combination therapy for MAC, but
azithromycin is equally efficacious and may cause fewer
gastrointestinal adverse effects and drug interactions. In
particular, clarithromycin should not be combined with
efavirenz because the interaction will result in decreased
efavirenz drug concentrations.
Rifabutin has significant interactions with many drugs,
including ARV medications and therefore dosage adjustments
or alternative agents may be needed (Table 1).