Intravenous Liposomal Amphotericin as an Adjunct to Fluconazole in Pediatric Patients With Central Nervous System Coccidioidomycosis: A Single-Center Case Series

Coccidioidomycosis is a fungal infection endemic to the southwestern United States. Central nervous system (CNS) coccidioidomycosis is a severe manifestation that requires lifelong antifungal therapy. While fluconazole is currently recommended as the initial therapy in pediatric patients, a rise in reports of fluconazole failure has led to use of alternative treatment approaches. In this paper, we evaluated our institutional preference to use intravenous (IV) liposomal amphotericin B (L-AmB) as part of the initial therapy for pediatric CNS coccidioidomycosis.

We conducted a retrospective case series of pediatric patients diagnosed with CNS coccidioidomycosis between 2010 and 2024. Clinical presentation, diagnostics, treatment strategies, and outcomes were analyzed.

Among 10 patients, 6 had mild initial symptoms of fevers and/or headaches, while 4 had more severe initial presentations, including focal deficits, seizures, or altered mental status. All severe cases received immediate IV L-AmB and fluconazole (+IV L-AmB); 75% were discharged with improvement. The 2 mild cases that received early +IV L-AmB had uncomplicated courses, while 2 of the 4 mild cases initially treated with fluconazole alone progressed to severe disease. Over an average follow-up of 4.5 years, 5 patients were fully functional without neurologic deficits, 2 had mild residual deficits, and 3 died. Relapse occurred in all but 1 patient. Patients receiving early +IV L-AmB trended toward shorter hospitalizations, lower disease progression rates, and delayed disease relapse.

Our institutional experience with IV L-AmB in combination with fluconazole for the initial management of pediatric CNS coccidioidomycosis suggests that +IV L-AmB may help reduce disease progression and improve symptom resolution with mild and transient side effects, although the findings of this case series should be interpreted cautiously due to the small cohort size, limited generalizability, and potential confounding factors.