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.