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A. Characteristics navigator

  1. Opportunistic fungal pathogen
  2. Transmission
    1. Encapsulated yeast occurring widely in nature
    2. Route of entry is usually via inhalation
    3. Usually asymptomatic infection
  3. May cause asymptomatic low grade pneumonia or pulmonary nodules
  4. Symptomatic infection unusual in absence of immunosuppression
  5. Most common cause of meningitis in AIDs
    1. Infection usually appears in late stage AIDS (CD4<200/µL)
    2. Typically causes meningitis
    3. Disseminated disease possible
  6. Also occurs in solid organ transplantation with immunosuppression [1]

B. Symptoms navigator

  1. Somewhat atypical for meningitis
    1. Headache is usually present
    2. Meningismus is often absent
    3. Altered mental status
  2. Fever - variable
  3. Focal neurologic findings are variable
  4. Pulmonary disease often with accompanying meningitis [2]
  5. Osteomyelitis can also occur, usually with disseminated disease [3]

C. Diagnosisnavigator

  1. Cerebrospinal Fluid (CSF) analysis
    1. Leukocytosis (lymphocytosis)
    2. Elevated CSF protein
    3. Encircled cocci on Gram or India Ink Stain of CSF
    4. CSF cultures may be positive
    5. Elevated CSF pressure (particularly in HIV) is an increased risk factor for death [1,4]
  2. Other Diagnostic Tests
    1. Serum cryptococcal antigen positive in >90% of cases
    2. Blood cultures may be positive
    3. CT scan to rule out other CNS pathology (including toxoplasmosis, PML)
  3. Pulmonary Radiographic Patterns [2]
    1. Diffuse parenchymal involvement (consolidation)
    2. Interstitial infiltrates
    3. Miliary pattern
    4. Cavitation may occur

D. Treatment navigator

  1. Usually divided into induction phase and consolidation (clearing)
    1. Amphotericin B (ABD) 0.7mg/kg/d IV x 2-12 weeks is preferred for induction therapy
    2. Consider adding 5-flucytosine (5-FC) 100mg/kg/d divided q6 hours [1,4]
    3. ABD + 5-FC had most rapid rate of clearance of cryptococcal meningitis in patients with HIV, compared with ABD alone, ABD+fluconazole, or ABD+5-FC+fluconazole [5]
    4. Therefore, induction therapy with for 14 days with ABD+5-FC recommended in HIV [5]
  2. Fluconazole 400-600mg po qd (divided)
    1. Enters CSF well, but has reduced efficacy for induction phase compared to amphotericin
    2. One study showed better activity of fluconazole, but this used low dose amphotericin
    3. Chronic suppression with fluconazole 200mg qd is more effective than amphotericin
    4. Fluconazole is better tolerated than amphotericin
    5. Itraconazole is slightly less effective than fluconazole as consolidation therapy [4]
  3. May need repeated lumbar punctures or shunt placement if increased intracranial pressure
  4. Lifelong suppression of disease with fluconazole or amphotericin is required

References navigator

  1. Fishman JA, Gonzalez RG, Branda JA. 2008. NEJM. 358(15):1604 (Case Record) abstract
  2. McGowen K and Mark EJ. 2002. NEJM. 347(7):517 (Case Record) abstract
  3. Lai KK and Rosenberg AE. 1999. NEJM. 340(25):1981
  4. van der Horst CM, Saag MS, Cloud GA, 1997. NEJM. 337(1):15 abstract
  5. Brouwer AE, Rajanuwong A, Chierakul W, et al. 2004. Lancet. 363(9423):1764 abstract