1401. Minimal Cerebrospinal Concentration of Miltefosine Despite Therapeutic Plasma Levels during the Treatment of Amebic Encephalitis

BACKGROUND: Miltefosine is an alkylphosphocholine compound used primarily for the treatment of leishmaniasis that also demonstrates in vitro and in vivo anti-amebic activity against Acanthamoeba species. As such, recommendations for treatment of amebic encephalitis generally include miltefosine therapy. Data support a minimum amebicidal concentration (MAC) of at least 16 μg/mL is required for most Acanthamoeba species. Given the high mortality associated with amebic encephalitis and a paucity of data regarding miltefosine levels in the plasma and cerebrospinal fluid (CSF) in vivo, we sought to determine whether a patient being treated with oral miltefosine at a higher-than-recommended dose obtained therapeutic plasma and CSF concentrations. METHODS: A patient with brain-biopsy-confirmed Acanthamoeba encephalitis was initiated on miltefosine 50mg by mouth every 6 hours (q6h), a higher frequency of therapy than recommended in the scant available literature (which suggests doses of 50 mg every 8 hours). Plasma and CSF miltefosine concentrations were collected on day 7 of treatment. CSF was collected via an external ventricular drain over a period of 1 hour. The quantification of miltefosine was performed using a Waters Xevo TQ-S triple quadrupole mass spectrometer coupled with a Waters Acquity UPLC I-class system. RESULTS: The trough plasma and CSF concentrations (taken 8 hours post-dose) were 16.2 and 0.007 µg/mL, respectively, resulting in a miltefosine plasma to CSF ratio of 2,440:1 µg/mL. The patient had no adverse reactions during the initial course of miltefosine therapy, though ultimately succumbed to the disease. CONCLUSION: This is the first report to describe plasma and CSF concentrations after administration of miltefosine 50mg q6h for the treatment of amebic encephalitis. The administration of miltefosine 50mg q6h resulted in plasma concentrations at the suggested MAC for Acanthamoebaspp. However, the miltefosine CSF concentration was extremely low compared with the plasma level and did not reach amebicidal concentrations. While miltefosine human brain parenchyma concentrations have yet to be described in the literature, this case questions if oral miltefosine is adequate to veritably treat patients with amebic encephalitis. DISCLOSURES: All authors: No reported disclosures.