Mycobacterium Avium Complex (MAC) (Mycobacterium Avium-Intracellulare = MAI)

Epidemiology

  • Incidence: MAC is the most common of the non-tuberculous mycobacteria to cause disease in humans
  • Peak Area: southeast USA
  • Prior to AIDS epidemic, 85-90% of all MAC isolates were from the lungs

Microbiology

  • Serotypes 4 and 8: cause most cases of HIV-associated cases
  • MAC causes disease in chickens, birds, swine, cattle, and non-human primates (animals may serve as reservoirs, but there is no known link between animal and human cases)
  • Environmental Sources
    • Soil
    • Animal Bedding
    • Plants
    • Standing Fresh Water
    • Salt Water

Physiology

Primary Acquisition of Mycobacterium Avium Complex (MAC), Probably Via the Gastrointestinal Tract (and Occasionally Via the Lungs)

  • Infection is Not Believed to Result from Reactivation
  • Source of MAC Infection in AIDS: given observation that airway and gastrointestinal tract colonization increase the future risk of MAC bacteremia in AIDS (with CD4 <50), it is likely that organism is already present and gains access to bloodstream with progressive decline in immune function (suggests that environmental acquisition of MAC is less likely)

Mechanisms Which May Increase the Risk of Pulmonary Non-Tuberculous Mycobacteria [MEDLINE]

  • Impaired nNO
  • Impaired Ciliary Beat Frequency
  • Impaired Toll-Like Receptor (TLR) Responses

Diagnosis

Complete Blood Count (CBC) (see Complete Blood Count, [[Complete Blood Count]])

Serum Immunoglobulin

  • Hypergammaglobulinemia

Bone Marrow Biopsy

  • Cultures may be positive
  • AFB are often found within foamy macrophages/histiocytes
  • Usually absent or poorly formed granulomas

Lymph Node Biopsy

  • Cultures may be positive

Liver Biopsy

  • Cultures may be positive

Blood Culture

  • May be positive
  • Preferred method of obtaining diagnosis in AIDS-related cases
  • Most frequent source of positive cultures in AIDS cases

Stool MAC Smears and Cultures

  • Frequently positive in AIDS cases

Intestinal Biopsy

  • Macrophages packed with MAC (may resemble Whipple’s disease)

ATS Criteria for Diagnosis of Non-Tuberculous Mycobacterial Disease (1997)

Clinical Criteria

  • Compatible Symptoms
    • Cough (see Cough, [[Cough]]): common
    • Deterioration in Clinical Status: if prior disease is present
    • Dyspnea (see Dyspnea, [[Dyspnea]])
    • Fatigue (see Fatigue, [[Fatigue]]): common
    • Hemoptysis (see Hemoptysis, [[Hemoptysis]])
    • Weight Loss (see Weight Loss, [[Weight Loss]])
  • Reasonable Exclusion of Other Lung Diseases

Radiographic Criteria

Bacteriologic Criteria (At Least 1 of the Following)

  • At Least 3 Sputum/Bronchoalveolar Lavage (BAL) Samples Within 1 Year
    • 3 Positive Cultures with Negative AFB Smears
    • 2 Positive Cultures with 1 Positive AFB Smear
  • Single Bronchoalveolar Lavage (BAL)
    • Positive Culture with 2+, 3+, or 4+ Growth: needs to only be 1+ growth in immunocompromised HIV-negative patients
    • Positive Culture with 2+, 3+, or 4+ AFB Smear
  • Tissue Biopsy
    • Any Growth from Bronchopulmonary Tissue Biopsy
    • Granuloma and/or AFB on Lung Biopsy with >1 Positive Sputum or Bronchoalveolar Lavage (BAL) Culture
    • Any Growth From Usually Sterile Extrapulmonary Site

Clinical Presentation-Hot Tub Lung/Swimming Pool Lung (Variants of Hypersensitivity Pneumonitis, HP) (see Hypersensitivity Pneumonitis, [[Hypersensitivity Pneumonitis]])

Epidemiology

  • Typically Immunocompetent Patient

Diagnosis

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Clinical

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Treatment


Clinical Presentation-Pulmonary MAC (Non-Immunocompromised Patient)

Epidemiology

Diagnosis

  • CXR/Chest CT
    • Multifocal nodular disease: female predominance
    • Upper lobe cavitary disease: male predominance
    • Bronchiectasis with/without centrilobular nodules (around ectatic bronchi)
  • Sputum Culture/Sensitivity positive MAC cultures
    • The more cultures that are positive, the more likely it is responsible for disease
  • Bronchoscopy
    • Bronchoalveolar Lavage (BAL): cultures may be positive for MAC (does not indicate invasive or disseminated disease)
      • Organism grow slowly and can be identified by the fact that it is non-pigmented and niacin-negative
    • Endobronchial MAC: appears as submucosal “pearls”
    • Endobronchial Biopsy (EBB): positive

Clinical

  • Cavitary/Non-Cavitary Pneumonia (see Pneumonia, [[Pneumonia]] and Cystic-Cavitary Lung Lesions, [[Cystic-Cavitary Lung Lesions]])
    • Cough (see Cough, [[Cough]])
    • Low-Grade Fever (see Fever, [[Fever]])
    • Malaise
    • Hemoptysis (see Hemoptysis, [[Hemoptysis]])
    • Lady Windermere Syndrome (from Oscar Wilde’s play Lady Windermere’s Fan): MAC occurring in typical location of lingula or RML in a middle-aged female
  • Cavitary/Non-Cavitary Lung Nodules (see Lung Nodule or Mass, [[Lung Nodule or Mass]] and Cystic-Cavitary Lung Lesions, [[Cystic-Cavitary Lung Lesions]])
  • Endobronchial MAC (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
    • Appears as submucosal “pearls”
    • Uncommon presentation
  • Extrapulmonary Dissemination: uncommon

Treatment

Medical Therapy

  • 3-Drug Regimen (Macrolide Agent + Rifamycin agent + Ethambutol)
    • Macrolide (see Macrolides, [[Macrolides]])
    • Rifamycin Group Antibiotic
      • Rifabutin (see Rifabutin, [[Rifabutin]])
        • Monitor patients receiving both clarithromycin + rifabutin for uveitis and with LFT’s/platelet count/WBC count
      • Rifampin (see Rifampin, [[Rifampin]])
    • Ethambutol (see Ethambutol, [[Ethambutol]])
      • Monitor patient for visual loss during therapy
  • Clinical Efficacy in Nodular/Bronchiectatic MAC [MEDLINE]
    • Macrolide-Based Regimens Demonstrate Favorable Microbiologic Outcomes Without Promotion of Macrolide Resistance
    • Intermittent (3x/wk) Macrolide-Based Regimens are Effective and are Better Tolerated Than Daily Therapy: no difference in sputum conversion or the need to discontinue therapy

Surgical Lung Resection

  • Indications: good surgical candidates with localized MAC who do not respond to antibiotics alone
    • Ideally, sputum should be converted to negative prior to surgery
    • If sputum does not convert by 4 mo, (or if by 2-3 mo there is no decrease in the number of organisms), surgery should be carried out

Clinical Presentation-Pulmonary MAC (Immunocompromised Patient)

Epidemiology

Clinical

Treatment

Medical Therapy

  • 3-Drug Regimen (Macrolide Agent + Rifamycin agent + Ethambutol)
    • Macrolide (see Macrolides, [[Macrolides]])
    • Rifamycin Group Antibiotic
      • Rifabutin (see Rifabutin, [[Rifabutin]])
        • Monitor patients receiving both clarithromycin + rifabutin for uveitis and with LFT’s/platelet count/WBC count
      • Rifampin (see Rifampin, [[Rifampin]])
    • Ethambutol (see Ethambutol, [[Ethambutol]])
      • Monitor patient for visual loss during therapy
  • Clinical Efficacy in Nodular/Bronchiectatic MAC [MEDLINE]
    • Macrolide-Based Regimens Demonstrate Favorable Microbiologic Outcomes Without Promotion of Macrolide Resistance
    • Intermittent (3x/wk) Macrolide-Based Regimens are Effective and are Better Tolerated Than Daily Therapy: no difference in sputum conversion or the need to discontinue therapy

Surgical Lung Resection

  • Indications: good surgical candidates with localized MAC who do not respond to antibiotics alone
    • Ideally, sputum should be converted to negative prior to surgery
    • If sputum does not convert by 4 mo, (or if by 2-3 mo there is no decrease in the number of organisms), surgery should be carried out

Clinical Presentation- Pulmonary MAC (AIDS Patient)

Epidemiology

  • MAC in AIDS is usually a systemic disease that does not involve the lungs
  • In AIDS, source of infection is not clear, no clear environmental sources have been identified
  • MAC occurs in 15-24% of AIDS cases
  • On average, MAC occurs 7-15 months after AIDS diagnosis is made
  • Risk Factor in AIDS: CD4 <200/┬ÁL

Physiology

  • Significance of Airway Colonization: presence of airway colonization (with negative blood cultures) increases risk of future dissemination in AIDS with CD4 <50 (83% developed MAC bacteremia within 10 months)
    • Suggests that lungs are a portal for entry

Clinical Manifestations

Treatment

  • Preferred Regimen: Macrolide + Ethambutol + Rifabutin +/- Streptomycin for 15-24 months
    • Single agent therapy with Macrolide leads to resistance (usually several months into therapy) and recurrent symptoms within 8-12 weeks
    • These agents decrease blood colony counts and systemic symptoms
    • Monitor patients receiving both Clarithro + Rifabutin for uveitis, LFT s, platelet counts, and WBC counts
    • Monitor patients on Ethambutol for visual loss
  • Surgical Lung Resection: can be considered for good surgical candidates with localized MAC who do not respond to antibiotics alone
    • Ideally, sputum should be converted to negative prior to surgery
    • If sputum does not convert by 4 months, (or if by 2-3 months there is no decrease in the number of organisms), surgery should be carried out

Clinical Presentation-MAC Lymphadenitis

Epidemiology

  • Age Group: occurs almost exclusively in children between 1-5 y/o

Diagnosis

  • Lymph Node Biopsy/Aspiration of Soft Node: best diagnostic procedure

Clinical

  • Painless Swelling of Single or Grouped Lymph Nodes: similar to tuberculous lymphadenitis
    • Most commonly in high anterior cervical chain
    • May produce fistulas
  • Systemic Symptoms/Signs are Uncommon

Treatment

  • Surgical Resection of Affected Nodes: indicated
  • Antibiotics: seem to have little benefit (however, macrolide-containing regimens have not been tested)

Clinical Presentation-Disseminated MAC

Epidemiology

  • Disseminated MAC was rare prior to AIDS epidemic
  • Presence of MAC in AIDS significantly decreases life expectancy and quality of life
  • Risk Factors for Dissemination
    • AIDS (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]])
      • MAC disease occurs in 19% of AIDS patients with CD4 <250
      • MAC occurs in 50% of AIDS cases at 30 months of follow-up (almost all had CD4 <60 at time of study entry)
      • Airway or GI tract colonization increases the risk of future MAC bacteremia (in AIDS with CD4 <50)
      • HAART and MAC prophylaxis (with clarithromycin, azithromycin, or rifabutin) decrease the incidence of MAC in AIDS
    • Immunocompromised Hosts: steroids are commonly associated
    • Children

Diagnosis

  • Sputum c/s: may be positive (positivity does not indicate invasive/disseminated disease)

Clinical

  • HIV-Negative Immunocompromised Patient
    • Abnormal Chest X-Ray: 65% of cases
    • Bone Lesions: most cases
    • Fever (see Fever, [[Fever]]): 54% of cases
    • Hepatomegaly (see Hepatomegaly, [[Hepatomegaly]]): 43% of cases
    • Local Pain Related to Site of Involvement: 32% of cases
    • Lymphadenopathy (see Lymphadenopathy, [[Lymphadenopathy]]): 43% of cases
    • Splenomegaly (see Splenomegaly, [[Splenomegaly]]): 35% of cases
    • Weight Loss (see Weight Loss, [[Weight Loss]]): 32% of cases
  • HIV-Positive AIDS Patient

Treatment

  • Disseminated MAC in AIDS: treatment improves survival and decreases symptoms

Effect of Immune Reconstitution Inflammatory Syndrome (IRIS) (see Immune Reconstitution Inflammatory Syndrome, [[Immune Reconstitution Inflammatory Syndrome]])

  • Immune reconstitution usually occurs within 6 months after start of HAART therapy and may paradoxically worsen disease, worsen disease from prior clinically latent infection, or result in an exaggerated inflammatory response
    • Disease may appear to worsen with tissue biopsies demonstrating necrosis (with sterile cultures)
    • NSAIDS may decrease the paradoxical inflammatory response

References

  • Mycobacterium avium complex spinal epidural abscess in an HIV patient. Australas Radiol. 1999 Nov;43(4):554-7 [MEDLINE]
  • Pulmonary nontuberculous mycobacterial disease prevalence and clinical features: an emerging public health disease. Am J Respir Crit Care Med 2010;182:977-982 [MEDLINE]
  • Abnormal nasal nitric oxide production, ciliary beat frequency, and toll-like receptor response in pulmonary nontuberculous mycobacterial disease epithelium. Am J Respir Crit Care Med 2013;187:1374-1381 [MEDLINE]

  • Macrolide/azalide therapy for nodular/bronchiectatic Mycobacterium avium complex lung disease. Chest 2014;146:276-282 [MEDLINE]

  • Nontuberculous mycobacteria in cystic fibrosis and non-cystic fibrosis bronchiectasis. Semin Respir Crit Care Med. 2015 Apr;36(2):217-24. doi: 10.1055/s-0035-1546751. Epub 2015 Mar 31 [MEDLINE]