Fungal Infections - Cryptococcus Meningitis (CM)

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CM is the most common form of fungal meningitis worldwide. It often develops in patients who are  immune  compromised  e.g.,  HIV-positive  patients  with  low  CD4  cell  count,  diabetic  mellitus  and  iatrogenic immunosuppression, as in post organ transplant patients. 

Clinical features 

  • Headache, fever, intolerance to light and sound
  • Neck  stiffness,  vomiting,  seizures, deafness, impaired vision
  • In advanced stages it may present with confusion
  • Altered mental status that may progress to coma

Investigations 

  • CSF gram stain
  • CSF India Ink stain test
  • Serum or CSF Cryptococcus antigen (CrAg) test
  • CSF cultures
  • Contrast brain MRI
    • may demonstrate cryptococcomas
    • assist to rule out differential diagnoses

Pharmacological Treatment 

The treatment should be done in 3 phases: 

Phase 1: Induction phase 

S: amphotericin B (IV) 0.7-1mg/kg/day 

AND 

S: 5 flucytosine (PO)100mg/kg/day for 7days followed by 1 week of 

AND 

A: fluconazole (PO): Adult 1200mg/day

Children/adolescents 2mg/kg/day, up to a maximum dose of 800mg daily 

In the absence of flucytosine, alternative therapy should be: 

S: amphotericin B (IV) if available give 3-6mg/kg for 10days 

AND 

A: fluconazole (PO) 1200mg once daily for 14days 

OR 

C: fluconazole (IV) 1200mg once daily for 14days 

Phase 2: Consolidation phase 

A: fluconazole (PO) 800mg/day for 8weeks or until CSF is sterile

Phase 3: Maintenance phase 

A: fluconazole (PO) 200mg 24hourly for 1year 

Discontinue maintenance treatment if CD4 ≥100 with undetectable (<50 copies), viral load or CD4 ≥  200 if viral load monitoring not available. 

Note:  

  • It  is  recommended  to  initiate  ART  5  weeks  after initiation of Cryptococcal meningitis treatment in ART naïve patient to prevent IRIS and reduce mortality
  • Monitor creatinine, BUN, serum potassium and magnesium in all patients on Amphotericin B every 24hours

Non-pharmacological Treatment 

  • Refer to section on bacterial meningitis in unconscious patients
  • Perform  serial  lumbar  puncture  for  management  of  increased  ICP  in  cryptococcal meningitis.  Opening  pressure  should  be  measured  during  LP  and  therapeutic  CSF drainage done (20-30ml per session) for pressures >25cm H2O.
  • Failure  to  control  ICP  after  several  LPs  (recommended  3  attempts)  should  prompt neurosurgical evaluation for ventriculoperitoneal shunt insertion to divert CSF

Note: The usage of mannitol, hypertonic saline, acetazolamide, or corticosteroids to manage increased  ICP in Cryptococcal meningitis is ineffective and NOT recommended.