Infection in Immunocompromised Hosts

Immunocompromise Basics - Setting the Stage

• Definition: Immune system's ↓ ability to fight infections & malignancies. Understanding this is crucial for risk stratification & guiding prophylactic/empirical therapy.
• Etiology:
  • Primary (Congenital): Rare genetic defects (e.g., SCID, CVID, DiGeorge Syndrome).
  • Secondary (Acquired): More prevalent; develops due to external factors.
    • HIV/AIDS (CD4 count < 200 cells/µL defines AIDS).
    • Hematological malignancies (leukemia, lymphoma) & solid tumors.
    • Solid organ or hematopoietic stem cell transplant recipients.
    • Immunosuppressive therapy: Corticosteroids (e.g., prednisone ≥20mg/day for ≥2 weeks), chemotherapy, biologics (e.g., TNF-α inhibitors).
    • Chronic diseases: Diabetes mellitus, chronic kidney disease, malnutrition, asplenia.
• Key Cellular Deficits & Implications:
  • Neutropenia: Absolute Neutrophil Count (ANC) < 1500/µL; severe if < 500/µL (↑ risk of bacterial/fungal infections).
  • Lymphopenia: T-cell defects (cellular immunity) → opportunistic infections (fungi, viruses, protozoa). B-cell defects (humoral immunity) → sinopulmonary bacterial infections.

⭐ HIV infection is a major cause of acquired immunodeficiency globally, leading to a spectrum of opportunistic infections as CD4 count declines below 200 cells/µL (AIDS-defining).

Defect-Pathogen Links - Know Your Enemy

Febrile Neutropenia - Fever Alarm!

• Definition: Fever (single oral T ≥ 38.3°C or T ≥ 38.0°C sustained for ≥1 hr) + Neutropenia (ANC < 500/mm³, or < 1000/mm³ with predicted nadir < 500/mm³).
• Risk Stratification:
  • MASCC Score: Low risk (≥21), High risk (<21).
  • High risk criteria also include: prolonged neutropenia (>7 days), significant comorbidities.
• Initial Management: Empiric broad-spectrum antibiotics within 1 hour.
  • High Risk: IV anti-pseudomonal β-lactam (e.g., Cefepime, Piperacillin-Tazobactam, Meropenem).
  • Low Risk: Consider oral (e.g., Ciprofloxacin + Amoxicillin-Clavulanate) or IV.
• Common Pathogens: Pseudomonas, E. coli, Klebsiella, Staphylococcus, Streptococcus.

⭐ Empiric antibiotic therapy must cover Pseudomonas aeruginosa.

Prophylaxis Strategies - Defense First!

• Goal: Prevent Opportunistic Infections (OIs) in vulnerable hosts.
• PCP (Pneumocystis jirovecii Pneumonia):
  • TMP-SMX (preferred).
  • Indications: HIV CD4 < 200/μL; post-transplant; prolonged high-dose corticosteroids.
• Toxoplasmosis:
  • TMP-SMX for Toxoplasma gondii IgG+ HIV patients, CD4 < 100/μL.
• MAC (Mycobacterium Avium Complex):
  • Azithromycin or Clarithromycin for HIV CD4 < 50/μL.
• Fungal Infections:
  • Antifungals (e.g., Fluconazole, Posaconazole) for HSCT, prolonged neutropenia.
• Viral (CMV, HSV/VZV):
  • Antivirals (e.g., Ganciclovir, Acyclovir) post-transplant, severe T-cell defects.
• Vaccinations:
  • Essential: Pneumococcal, Influenza (inactivated), Hepatitis B.
  • ⚠️ Avoid live vaccines if severely immunocompromised.

⭐ TMP-SMX is cornerstone for PCP prophylaxis; also covers Toxoplasmosis & Nocardiosis.

High‑Yield Points - ⚡ Biggest Takeaways

• Neutropenia (ANC < 500/mm³): risk of bacterial (Pseudomonas) & fungal (Aspergillus, Candida) infections.
• T-cell defects (HIV, steroids): risk of PJP, CMV, Cryptococcus, Toxoplasma.
• HIV CD4 counts guide OI risk: PJP <200, Toxo/Crypto <100, CMV/MAC <50.
• Key prophylaxis: TMP-SMX for PJP/Toxo; antifungals for severe neutropenia.
• Invasive aspergillosis: halo/crescent sign (CT), treat with voriconazole.
• PJP: diffuse infiltrates, ↑LDH, treat/prophylax with TMP-SMX.
• Cryptococcal meningitis: India ink/antigen positive, treat with Amphotericin B + Flucytosine.