Survival improvement in coccidioidal meningitis by high-dose intrathecal amphotericin B

Abstract

Eleven patients with coccidioidal meningitis were treated with high individual doses (1.0 to 1.5 mg) of intrathecal amphotericin B mixed with 25 to 50 mg of hydrocortisone in an attempt to reach a dose of 12 mg per month for at least two consecutive months. Patients received a mean intrathecal dose of amphotericin B of 82 mg (range, 40 to 157 mg) and 2.4 g intravenously (range, 1.0 to 3.5 g). No deaths related to disease or treatment occurred, and overall survival was 91% during an average follow-up period of 75 months (range, 30 to 137 months). Comparative analysis with eight well-known series in the literature reveals that our survival rate and follow-up time are significantly greater than the more recent series (1977-1981). Rank correlation and linear regression showed that the mean intrathecal dose of amphotericin B used in all series corresponds well with mean survival time. Our clinical results and analysis of the literature suggest that intrathecal amphotericin B administered at a high dose rate of 0.75 mg (or greater) three times per week promptly reaching 20 mg and a total surpassing 40 mg is associated with significantly enhanced survival rates.