Mycobacterium avium complex (MAC), disseminated
Timothy R. Sterling, M.D.
- MAC incidence lower in Africa than USA. In Africa 5 - 10% of hospitalized patients with HIV & wasting have MAC in blood Cx
- Sx: weight loss, fevers, diarrhea, leukopenia
- Labs: CD4 rarely >50
- Dx: mycobacterial Cx and speciation not generally available in Zambia, use clinical judgement
- Consider empiric therapy in pt with CD4<50 with wasting, fever, no lymphadenopathy, and no evidence of TB or failure to respond to TB therapy.
- Primary prophylaxis for MAC not recommended because of lower incidence in Africa
Zambia Information Author: Christopher Hoffmann, MD, MPH
- Mode of transmission, acquisition unclear. May be inhaled and/or ingested.
- May be less common in Africa than developed world.
M. avium, M. intracellulare ubiquitous in environment: water, soil
- Colonization of GI tract, lungs often precedes disseminated disease
- Seen almost exclusively in HIV+ pts with CD4 <50; also seen in HIV-negative pts s with IFN-gamma receptor deficiency, IL-12 or IL-12 receptor deficiency
- Signs/Sx: fevers, night sweats, weight loss, abdominal pain, diarrhea.
- Lab findings: anemia, elevated alkaline phosphatase
- Lung disease uncommon, but can occur
- Immune reconstitution disease can occur in patients on HAART: Focal disease (e.g., lymphadenitis, spinal osteomyelitis) + constitutional Sx.
- Single blood Cx 90% sensitive; 2nd Cx increases sensitivity slightly
- Requires 10-21 days for growth in Cx (e.g., BACTEC)
- Cx from other sterile body sites useful (e.g., bone, lymph node). Positive Cx from sputum or stool often represent colonization rather than infection. Cx of lung Bx specimen generally felt to represent infection.
Clarithromycin 500 mg bid + ethambutol 15 mg/kg qd. Addition of rifabutin 300 mg qd may improve survival (conflicting data--see refs) and decrease risk of macrolide resistance. Consider adding if CD4 < 50, high mycobacterial load, or absence of effective ART
Azithromycin 500-600 mg qd + ethambutol 15 mg/kg qd
Clarithromycin levels increased by indinavir, ritonavir, saquinavir
Clarithromycin levels decreased by rifabutin; rifabutin levels increased by clarithromycin
- Caution with clarithromycin + efavirenz: high rates of rash
- Treatment may be stopped in asymptomatic pts with >12 mos of therapy if CD4 >100 for >6 mos. Restart when CD4 <100.
- Do not use clofazamine: associated with increased mortality risk
- Consider a fluoroquinolone and aminoglycoside (amikacin or streptomycin) for drug-resistant disease.
- Drug susceptibility testing useful only for macrolides in persons with prior macrolide exposure
- Caution with rifabutin: drug interactions with PIs, NNRTI, itraconazole, etc
- Indicated when CD4 <50
- Preferred: azithromycin 1200 mg q wk or clarithromycin 500 mg bid
- Alternative: rifabutin 300 mg qd.
- Combination of azithromycin + rifabutin effective, but greater toxicity
- Prophylaxis can be stopped when CD4 >100 for >3 mos; restart when CD4 <100
- Combination of clarithromycin + rifabutin no more effective than clarithromycin alone, but higher rates of adverse effects; do not use this combination.
||Rarely used. Follow for nephrotoxicity, 8th cranial nerve toxicity
||Used most often for prophylaxis
||Used most often for active disease (in combination with ethambutol +/- rifabutin)
||Generally not used
||Consider monthly eye exam with chronic treatment
||Can generally adjust for drug interactions--not a reason to avoid