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Mycobacterium avium-complex (MAC, Mycobacterium avium intracellulare, MAI)

Etiology: (risk Factors) 1) immunodeficiency (most commonly AIDS) - HIV1 infection with CD4 count < 50/uL [3] - immune reconstitution inflammatory syndrome (IRIS) 2) underlying pulmonary disease a) COPD b) bronchiectasis c) cystic fibrosis d) alpha-1-antitrypsin deficiency e) prior pulmonary tuberculosis Epidemiology: 1) organism is ubiquitous in the environment 2) respiratory tract & GI tract are portals of entry 3) 18-44% of patients with AIDS will develop MAC without prophylaxis; 2% with effective antiviral therapy 4) white, middle-aged/elderly male smokers/COPD 5) non-smoking women over age 50 without underlying lung disease (Lady Windermere Syndrome) 6) most common nontuberculous mycobacterial infection [3] - most common cause of chronic lung infection worldwide [3] Pathology: 1) disseminated multiorgan infection - occurs in patients with HIV1 with CD4 counts < 50/uL & not received prophylaxis for MAC (see management) [3] 2) sustained bacteremia 3) generally late-stage HIV complication with CD4 < 50/mm3 4) localized disease syndrome (uncommon) a) hypersensitivity pneumonitis 'hot-tub lung' b) tuberculosis-like infection in elderly male smokers c) chronic right middle lobe syndrome, lingula infection & cough in elderly women (Lady Windermere syndrome) d) enteritis e) pericarditis f) osteomyelitis e) skin lesions g) soft tissue abscesses h) central nervous system lesions i) lymphadenitis [3] - lymph node acid-fast stain, with numerous mycobacteria growing within macrophages [3] Clinical manifestations: 1) fever 2) night sweats 3) chronic cough 4) weight loss 5) fatigue 6) wasting 7) diarrhea 8) abdominal pain 9) hepatosplenomegaly 10) intra-abdominal lymphadenopathy 11) resembles tuberculosis symptomatically 12) in IRIS, most often presents as a focal, inflammatory lymphadenitis ~ 4 weeks after initiating antiretroviral therapy [3] Laboratory: 1) complete blood count a) anemia (Hct < 30%) b) neutropenia 2) liver function tests - elevated alkaline phosphatase 3) sputum for acid-fast bacteria 4) sputum culture for Mycobacterium - repeat sputum culture if positive before treating - supposedly this will help distinguish infection for colonization (common) [3] 5) blood cultures 6) bone marrow biopsy & culture 7) antimicrobial sensitivities 8) Mycobacterium avium complex DNA 9) Mycobacterium avium complex rRNA 10) IFN-gamma release test is negative [3] Special laboratory: - bronchoalveolar lavage (BAL) Radiology: - resembles tuberculosis radiographically - nodular opacities with bronchiectasis in the right middle lobe on chest imaging (Lady Windermere syndrome) Complications: - immune reconstitution inflammatory syndrome occurs in AIDS patients with disseminated Mycobacterium avium complex [3] Management: 1) Lady Windermere syndrome or other immunocompetent adult - azithromycin, rifampin, & ethambutol three times weekly (MKSAP20) [3] - continue treatment >= 12 months after culture conversion (MKSAP20) [3] 2) pulmonary disease or disseminated infection with patients with CD4 count < 50/uL sufficient to warrant therapy ?? [3] a) organisms usually resistant to most conventional anti-mycobacterial agents* b) combination of 2 or 3 drugs 1] macrolide [3] a] clarithromycin 500 mg BID b] azithromycin 500 mg QD 2] ethambutol 25 mg/kg/day x 2 months, then 15 mg/kg/day + 3] with or without rifabutin 300 mg/day or rifampin 4] dosage 3 times weekly as effective as daily with fewer adverse effects [6] c) alternative agents 1] fluoroquinolone a] levofloxacin b] ciprofloxacin 500-750 mg BID 2] streptomycin 3] amikacin 10-15 mg/kg/day IV d) response may be expected after 2-8 weeks of therapy e) discontinue treatment after 12 months of successful treatment [4] 3) consider surgery for local or unresponsive disease 4) prophylaxis when CD4 count < 50/uL a) azithromycin 1200 mg weekly (prophylaxis of choice) b) clarithromycin 500 mg BID c) discontinue prophylaxis when CD4 count > 100/mm3 for 3 months [4] 5) empiric antibiotic therapy for Mycobacterial infection in a patients with advanced HIV infection a) isoniazid b) rifampin c) pyrazinamide d) ethambutol e) clarithromycin * Mycobacterium avium is frequently/generally resistant to isoniazid & rifampin.

Related

diagnosis of Mycobacterium avium intracellulare

Specific

Mycobacterium avium Mycobacterium avium paratuberculosis Mycobacterium intracellulare

General

Mycobacterium

Properties

KINGDOM: monera DIVISION: SCHIZOMYCETES

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 579
  2. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 723
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 20 American College of Physicians, Philadelphia 2025
  4. Journal Watch 22(20):150, 2002 Yeni PG et al, JAMA 288:222, 2002 Dybul M et al, Ann Intern Med 137:381, 2002 MMWR Recomm Rep 51:1-64, 2002 http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5107a1.htm Masur H et al, Ann Intern Med 137:435, 2002 http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5108a1.htm
  5. Kasperbauer SH, Daley CL. Diagnosis and treatment of infections due to Mycobacterium avium complex. Semin Respir Crit Care Med. 2008 Oct;29(5):569-76 PMID: 18810690
  6. Jeong B-H et al. Intermittent antibiotic therapy for nodular bronchiectatic Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2015 Jan 1; 191:96. PMID: 25393520 - Bag R and Griffith DE. Therapy for Mycobacteriium avium complex lung disease. It ain't perfect, but it's progress. Am J Respir Crit Care Med 2015 Jan 1; 191:14 PMID: 25551346
  7. NEJM JWatch Question of the Week. March 27, 2018 https://knowledgeplus.nejm.org/question-of-week/562/
  8. Ebihara T, Sasaki H. Bronchiectasis with Mycobacterium avium Complex Infection. N Engl J Med 2002; 346:1372 PMID: 11986411 Free full text http://www.nejm.org/doi/full/10.1056/NEJMicm010899
  9. Kasperbauer SH, Daley CL. Diagnosis and treatment of infections due to Mycobacterium avium complex. Semin Respir Crit Care Med 2008 Sep 24; 29:569 PMID: 18810690