Diagnosis>Opportunistic Infections>

PATHOGENS

• M. avium
• M. intracellulare
• Mode of transmission, acquisition unclear. May be inhaled and/or ingested.
• May be less common in Africa than developed world.

CLINICAL

• 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 ART: Focal disease (e.g., lymphadenitis, spinal osteomyelitis) + constitutional Sx.

DIAGNOSIS

• 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.

TREATMENT

• Clarithromycin 500 mg twice-daily + ethambutol 15 mg/kg once daily. Addition of rifabutin 300 mg once-daily 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 once-daily + ethambutol 15 mg/kg once-daily
• 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 (moxifloxacin, levofloxacin, or ciprofloxacin) 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; rule out disseminated MAC before initiating prophylaxis
• Preferred: azithromycin 1200 mg weekly or clarithromycin 500 mg twice-daily or azithromycin 600 mg twice-weekly
• Alternative: rifabutin 300 mg once-daily. First rule out active TB
• 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.

Drug Comments

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Azithromycin
• Mycobacterium spp.
• Toxicity & side effects: switching therapy (Zambia specific)