Makindo Medical Notes

🦠 Mycobacterium avium complex (MAC) infection is a common opportunistic infection in advanced HIV (CD4 <100 cells/mm³). It causes disseminated systemic illness with fever, weight loss, anaemia, and hepatosplenomegaly. Combination therapy with macrolide + ethambutol ± rifabutin and immune restoration (ART) are essential for management and prevention.

📘 About Mycobacterium avium Complex (MAC)

• MAC comprises Mycobacterium avium and Mycobacterium intracellulare, collectively called Mycobacterium avium–intracellulare (MAI).
• These are non-tuberculous mycobacteria (NTM) — environmental organisms found in soil, dust, and water.
• They rarely cause disease in immunocompetent hosts but are a major cause of morbidity in patients with advanced immunosuppression.

🧬 Aetiology & Risk Factors

• Profound immunocompromise:
  • Most cases occur with CD4 count <50–100 cells/mm³.
  • Seen in late HIV/AIDS, haematological malignancy, or post-chemotherapy immunosuppression.
• Environmental exposure: Organisms are ubiquitous; infection acquired via inhalation or ingestion rather than person-to-person transmission.
• Other risk groups: Chronic lung disease (e.g. bronchiectasis, COPD), especially older women — the so-called “Lady Windermere syndrome.”

🧠 Pathophysiology

• MAC invades macrophages and replicates intracellularly.
• Dissemination via lymphatics and bloodstream leads to multiorgan involvement — bone marrow, liver, spleen, and bowel.
• Poor granuloma formation due to impaired T-cell–mediated immunity → widespread disease rather than localised infection.

⚕️ Clinical Features

• Systemic: Fever, night sweats, weight loss, fatigue.
• Gastrointestinal: Chronic diarrhoea, abdominal pain, hepatosplenomegaly, elevated ALP.
• Respiratory: Cough, bronchiectasis, pulmonary nodules — often indolent (especially in non-HIV forms).
• Musculoskeletal: Osteomyelitis, tenosynovitis, synovitis.
• Disseminated disease: Bacteraemia with sepsis-like picture in advanced AIDS.

🔬 Investigations

• Laboratory:
  • Normocytic anaemia, raised ESR and ALP, mild leukocytosis.
  • Blood cultures (mycobacterial culture) often positive in disseminated disease.
• Microbiology:
  • Culture from blood, urine, sputum, stool, or bone marrow confirms diagnosis.
  • Speciation required to distinguish from *M. tuberculosis* complex.
• Imaging:
  • CT chest/abdomen: Generalised lymphadenopathy, hepatosplenomegaly, pulmonary nodules, or bronchiectasis.
  • Consider PET/CT if disseminated disease suspected to guide biopsy.

💊 Management

• Specialist (Infectious Disease or HIV) supervision is essential.
• First-line regimen:
  • Clarithromycin 500 mg BD or Azithromycin 500 mg OD
  • + Ethambutol 15 mg/kg/day PO
  • ± Rifabutin 300 mg/day (if not contraindicated or interacting with ART)
• Treatment duration: ≥12 months and until CD4 >100 cells/mm³ for ≥6 months on ART.
• Start ART: After 2 weeks of MAC therapy to reduce risk of immune reconstitution inflammatory syndrome (IRIS).
• Monitor: LFTs, visual acuity (ethambutol), and drug interactions (macrolides & rifamycins).

🧩 Prevention

• Primary prophylaxis (HIV):
  • For patients with CD4 <50 cells/mm³ not yet on ART — Azithromycin 1200 mg weekly or Clarithromycin 500 mg BD.
  • Stop once CD4 >100 for >3 months on ART.

⚠️ Complications

• Immune Reconstitution Inflammatory Syndrome (IRIS): paradoxical worsening after ART initiation due to immune recovery.
• Relapse if ART adherence poor or therapy duration inadequate.
• Drug toxicity: optic neuritis (ethambutol), hepatotoxicity, GI upset, and significant CYP interactions with macrolides and rifamycins.

📚 References

• BNF: Tuberculosis & Mycobacterial Infections
• British HIV Association (BHIVA) Guidelines on Opportunistic Infections, 2024.
• UpToDate: “Disseminated Mycobacterium avium complex infection in patients with HIV.”
• CDC HIV Opportunistic Infection Guidelines (2023 update).