What is a Mycobacterium Avium Complex (MAC) infection?

What is a MAC Infection?

MAC (Mycobacterium Avium Complex) infection is a disease caused by environmental nontuberculous mycobacteria found ubiquitously in water and soil that primarily causes either chronic pulmonary disease in immunocompetent hosts or disseminated infection in severely immunocompromised patients. 1, 2

Organism and Transmission

• MAC consists of nontuberculous mycobacteria that are ubiquitous in environmental sources, particularly water, soil, and biofilms 3
• Acquisition occurs through ingestion or inhalation of aerosols from environmental sources, including hot water pipes 4, 3
• There is no evidence of human-to-human or animal-to-human transmission 2

Clinical Presentations

MAC manifests differently depending on the host's immune status:

Pulmonary Disease in Immunocompetent Hosts

Two distinct forms occur:

• Fibrocavitary disease: Affects middle-aged male smokers with history of alcohol use, presenting with cavitary lung lesions 2
• Nodular bronchiectatic disease (Lady Windermere syndrome): Predominantly affects postmenopausal, nonsmoking white women in their seventh or eighth decade of life with no underlying immune compromise 1, 2

Clinical features of pulmonary MAC include:

• Chronic cough, often associated with fever and weight loss 1
• Insidious symptoms with several years between onset and diagnosis 1
• Radiographic findings show bronchiectasis and nodular densities, especially in the middle lobe and lingula 1
• CT scans reveal nodules distributed around peripheral vessels and airways, frequently with a tree-in-bud configuration 1
• Presence of granulomas in the airways indicates MAC infection is the primary disorder leading to progressive airway damage and bronchiectasis 1

Disseminated Disease in Immunocompromised Patients

Disseminated MAC occurs almost exclusively in severely immunocompromised patients:

• Affects patients with advanced HIV infection, typically with CD4 counts <50 cells/μL, with highest risk at CD4 <25 cells/μL 1, 2
• Approximately 40% of AIDS patients with CD4 <10 cells/μL developed disseminated MAC within 1 year in pre-antiretroviral era 1
• Over 90% of disseminated NTM infections in AIDS patients are caused by MAC, with >90% due to M. avium specifically 1

Clinical manifestations of disseminated MAC:

• Fever (80% of patients), night sweats (35%), and weight loss (25%) 1, 2
• Abdominal pain or diarrhea 1
• Physical findings include abdominal tenderness or hepatosplenomegaly, though palpable lymphadenopathy is uncommon 1

Laboratory abnormalities:

• Severe anemia with hematocrit <25% 1, 2
• Elevated alkaline phosphatase 1, 2
• Elevated lactate dehydrogenase 1, 2

Other Manifestations

• Cervical lymphadenitis: Most common form in children aged 1-5 years, affecting submandibular, submaxillary, cervical, or preauricular lymph nodes 1
• Immune reconstitution syndrome: Occurs in HIV patients who recently started antiretroviral therapy, presenting with suppurative lymphadenopathy, pulmonary infiltrates, soft tissue abscesses, or skin lesions 1
• Hypersensitivity pneumonitis (hot-tub lung): Related to MAC antigen exposure 1

Diagnosis

For disseminated MAC:

• Over 90% of patients have positive blood cultures, making this the primary diagnostic method 1
• For symptomatic patients with two negative blood cultures, biopsy and culture of bone marrow or liver may be indicated 1
• Lymph node excision for histopathology and culture is indicated for patients with lymphadenopathy 1

For pulmonary MAC:

• Diagnosis requires pulmonary symptoms, characteristic radiographic findings (nodular or cavitary opacities with multifocal bronchiectasis), plus positive cultures from two sputum specimens or one bronchoscopic specimen 3
• Sputum cultures are not sufficiently sensitive in many patients 1
• Bronchoscopic biopsies may be needed in patients with typical clinical and radiographic features 1

Treatment Principles

For pulmonary MAC:

• First-line therapy consists of a macrolide (clarithromycin or azithromycin) with ethambutol and a rifamycin (rifabutin or rifampin) 1, 3
• Three times weekly dosing for noncavitary disease; daily dosing with or without aminoglycoside for cavitary disease 3
• Treatment regimens are prolonged, often poorly tolerated, and patients frequently relapse 1
• Treatment success rate (defined as eradication without relapse) is approximately 55% with macrolide-containing regimens 4

For disseminated MAC in AIDS:

• Prophylaxis is indicated for patients with CD4 <50 cells/μL using clarithromycin, azithromycin, or rifabutin 1
• Treatment requires multidrug regimens including macrolides 1