›Fluconazole 400–800 mg/day orally
›Duration more than 1 year total
›Or itraconazole 200 mg twice daily per site of involvement
Antifungal therapy — coccidioidal meningitis
›Fluconazole high-dose — mainstay of meningitis treatment
›Fluconazole 800–1200 mg orally or IV once daily
›Lifelong therapy required
›Relapse occurs in 80% or more if discontinued
›Superior CNS penetration compared to itraconazole
›Itraconazole as alternative for fluconazole-refractory meningitis
›200 mg orally twice or three times daily
›Therapeutic drug monitoring required
›Intrathecal amphotericin B for refractory meningitis
›Amphotericin B deoxycholate intrathecal or intraventricular
›Experienced practitioner only
›Dose typically 0.01–0.5 mg in 10 mL CSF
›Via lumbar puncture or Ommaya reservoir
›Adjunct to systemic azole therapy
›VP shunt placement
›Indications
›Symptomatic communicating hydrocephalus
›Progressive ventricular enlargement on serial imaging
›Elevated opening pressure above 25 cmH2O with symptoms
›Surgical considerations
›Neurosurgical consultation urgent when hydrocephalus confirmed
›Shunt infection risk is an ongoing concern
Salvage and refractory disease
›Alternative triazoles for refractory disease
›Posaconazole extended-release
›300 mg orally twice daily on day 1, then 300 mg once daily
›Food enhances absorption
›QT prolongation monitoring required
›Voriconazole
›6 mg/kg IV every 12 hours for 2 doses, then 4 mg/kg IV every 12 hours
›Step down to 200–300 mg orally twice daily when tolerated
›Therapeutic drug monitoring — target trough 1–5.5 mcg/mL
›Photosensitivity and visual disturbances counseling
›Isavuconazole
›372 mg orally or IV every 8 hours for 6 doses (loading), then 372 mg once daily
›Good CNS penetration; QT shortening rather than prolongation
›Adjunctive immunotherapy
›IFN-gamma therapy for patients with IFN-gamma pathway defects
›Adjunctive dupilumab has shown success in refractory cases
›Immunodeficiency workup required before initiation
›Nephroprotection during amphotericin B
›Hydration protocol
›500–1000 mL saline before each dose
›Avoid concomitant nephrotoxins when possible
›Daily renal panel monitoring
›Electrolyte management
›Hypokalemia — replace with IV or oral potassium
›Hypomagnesemia — magnesium supplementation
›QT monitoring on azole therapy
›Baseline ECG before initiating fluconazole or voriconazole
›Repeat ECG if concurrent QT-prolonging medications added
›Target QTc below 500 ms