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Source: Carver PL. Invasive Fungal Infections. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. Accessed June 24, 2012.

  • Systemic fungal infection

  • Caused by ubiquitous encapsulated soil yeast Cryptococcus neoformans.

  • Acquired by inhalation.
  • Stimulates minimal inflammatory response in tissue.
  • Polysaccharide capsule appears to allow resistance to host phagocytosis.
  • Four serotypes of C. neoformans
  • Cell-mediated immunity plays major role in host defense.
    • 29–55% of patients with cryptococcal meningitis have predisposing condition.

  • C. neoformans found in soil, particularly in pigeon droppings
  • Incidence has risen; increased numbers of immunocompromised patients.
  • No geographic area of endemic focus

  • Immunocompromised patients
    • Malignancies
    • Diabetes
    • Chronic renal failure
    • Organ transplantation
    • Receiving immunosuppressive agents
    • AIDS

  • Disease may remain localized in lungs or disseminate to other tissues, particularly CNS, although skin can also be affected.

Signs and Symptoms

  • Primary cryptococcosis almost always occurs in lungs
    • Usually subclinical infection
    • Symptomatic infections resolve spontaneously
      • Cough
      • Rales
      • Shortness of breath
  • Cryptococcal meningitis
    • Asymptomatic in 10–12% of all patients
      • Non-AIDS patient
        • Fever
        • Headache
        • Nausea
        • Vomiting
        • Mental status changes
        • Neck stiffness
        • Photophobia
      • AIDS patient
        • Fever
        • Headache

Means of Confirmation and Diagnosis

  • Examination of cerebrospinal fluid (CSF)
    • Latex agglutination to detect antigens to C. neoformans
    • India ink smear of CSF detects ~60% of C. neoformans.
    • C. neoformans can be cultured in 96% of patients.

Laboratory Tests

  • Serologic testing: Latex agglutination
  • India ink smear of CSF
  • Cultures
  • Serum cryptococcal antigen


  • MRI more sensitive than CT to detect CNS abnormalities

Diagnostic Procedures

  • Lumbar puncture
    • Elevated opening pressure
    • CSF pleocytosis (usually lymphocytes)
    • Leukocytosis
    • Decreased CSF glucose
    • Elevated CSF protein
    • Positive cryptococcal antigen

Differential Diagnosis

  • Tuberculous meningitis
  • Other fungal infection
  • Neurosyphilis
  • Lyme meningitis

  • Resolution of signs and symptoms of infection
  • Cure infection

  • Nonimmunocompromised patients
    • Careful observation an option with asymptomatic, isolated pulmonary disease and no evidence of CNS disease.
    • Management of symptomatic infection in Table 1.
      • Combination of amphotericin B with flucytosine for 6 weeks
      • Alternative regimen: amphotericin B for 2 weeks, followed by fluconazole for additional 8–10 weeks
      • Optional: suppressive therapy with fluconazole for 6–12 months after completion of induction and consolidation therapy
  • Immunocompromised patients
    • Amphotericin B with flucytosine initial treatment of choice
    • After 2 weeks, consolidation therapy with either itraconazole orally or fluconazole orally administered for 8 weeks or until CSF cultures are negative.
    • Relapse of C. neoformans meningitis occurs in ~50% of AIDS patients after completion of primary therapy.
      • Lifelong therapy with fluconazole is recommended.

Table 1. Therapy of Cryptococcocosisa

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