Intrathecal Amphotericin B: A 60-Year Experience in Treating Coccidioidal Meningitis

Abstract

Coccidioidal meningitis (CM) is a devastating complication of coccidioidomycosis. Since the late 1950s, intrathecal (IT) amphotericin B deoxycholate (AmBd) has been successfully used to treat and often cure this disease, reducing mortality rates from 100% to approximately 30%. The introduction of azoles further revolutionized the treatment of coccidioidal infections. However, IT AmBd remains the only known curative option in the management of CM. While the use of IT AmBd is well described in many articles, few discuss the actual methods behind preparation, titration, and dosing strategies utilized. The practitioners at Kern Medical (Bakersfield, California) have >60 years of experience in the utilization of IT AmBd and the treatment of CM. This article describes the practice experience in the treatment of CM, preparation of IT AmBd, and the different dosing strategies used in regard to route of administration (ie, cisternal, lumbar, ventricular).

Antifungal Drugs: Special Problems Treating Central Nervous System Infections

“…Given the limitations of a systemic drug reaching the CNS, direct administration of antifungal agents into the CNS has been attempted. The majority of data with this approach is with administration of amphotericin B deoxycholate via the intrathecal route [56,57]. Recent experience has been gained with the lipid-based amphotericin B formulations [58,59] and administration of the deoxycholate preparation using implanted drug reservoirs [60].…”

“…Toxicities of direct drug administration in the CSF must also be considered. In the case of amphotericin B, nausea, vomiting and headache are most commonly reported, although more severe cases of neurotoxicity, including hearing loss and ataxia, have also been reported [57]. Therefore, to ensure optimal exposure this route of administration should be accompanied by systemic antifungal therapy.…”

Myelitis due to Coccidioidomycosis in an Immunocompetent Patient

“…They report successful treatment and cure of the disease and reduction in mortality rates from 100% to 30% while using intrathecal amphotericin B deoxycolate for treatment of coccidioidal meningitis. They consider it as the only known option in the management of coccidioidal meningitis [ 14 ]. After explanation of all risks and benefits of the treatment with amphotericin B to the patient, continuous amphotericin B infusion via Ommaya reservoir was recommended by the medical team; however, the patient has declined the therapy.…”

Patient With a 42-Year History of Coccidioidal Meningitis

“…He suffered auditory, but not vestibular, nerve damage related to intrathecal amphotericin B deoxycholate neurotoxicity. 5…”