Successful Control of Refractory Coccidioides Meningitis With MAT2203

Abstract Background Coccidioides meningitis is a life-threatening complication with Coccidioides spp that requires lifelong antifungal therapy. While some cases respond to azoles, others are refractory and require periodic treatment with intravenous and/or intrathecal (IT) amphotericin B. MAT2203 is a novel formulation of amphotericin B that uses a rolled phosphatidylserine lipid nanocrystal bilayer that is orally absorbed. MAT2203 has been successfully used to treat cryptococcal meningitis and Histoplasma meningitis. Case Presentation In 2017 a previously healthy construction worker developed coccidioidal pneumonia and meningitis and was treated with liposomal amphotericin B and oral fluconazole. His pneumonia resolved, but his meningitis worsened. Imaging showed vasculitis of his middle cerebral artery and arachnoiditis at the base of the brain and eventually throughout his spine. He required multiple changes in azoles and eventually an Ommaya reservoir so that he could receive periodic IT amphotericin B plus corticosteroids while continuing oral isavuconazole. Treatment response was monitored with symptoms, cerebral spinal fluid (CSF) cell counts, CSF Coccidioides antigen, and imaging. Frequency of IT treatment varied over the course of his illness from 3 times per week to monthly, increasing with symptom flares. A trial of the investigational antifungal olorofim also failed. In 2024, 1 month after his last dose of IT amphotericin B, the patient started treatment with MAT2203. After 6 months of MAT2203 (without any IT or intravenous amphotericin B), Coccidioides antigen in the ventricular CSF was undetectable for the first time and remained so with normalization of glucose and cell counts. Conclusions MAT2203 may offer an oral therapeutic option for refractory cases of Coccidioides meningitis.