Amphotericin B and imidazole therapy for coccidioidal meningitis in children.

Abstract

Coccidioidal meningitis is a fatal form of Coccidioides immitis infection. Amphotericin B (AMB) therapy has reduced mortality but is itself toxic, and experience with it in very young children is meager. We are treating six children for coccidioidal meningitis diagnosed at 19 to 74 months of age. All had acute hydrocephalus and ventriculitis. The first four patients were initially treated with AMB but were changed to imidazole therapy (miconazole and ketoconazole). In the last two patients therapy was begun with the imidazoles. Ommaya reservoirs for cisternal therapy have been of limited usefulness. AMB therapy has been limited by local and systemic toxicity and by failure in one case. All children have improved with 15 to 22 mg oral ketoconazole per kg per day and 3 to 5 mg intraventricular miconazole for instillation therapy, including those with noncommunicating hydrocephalus in whom the intraventricular drug does not reach the basilar cisterns. Peak concentrations of ketoconazole in ventricular fluid were 0.08 to 5.6 micrograms/ml. Shunt obstruction and bacterial superinfections have been the major causes of morbidity. Imidazole therapy of coccidioidal meningitis may be more effective than is AMB in young children, and it offers the advantages of fewer side effects and not requiring intrathecal or cisternal administration.