Imidazole therapy of coccidioidal meningitis in children.

Abstract

The mortality related to coccidioidal meningitis (CM) has been reduced since the introduction of amphotericin B therapy, but children with CM continue to suffer significant morbidity. Some of this is related to the toxicity of the drug. We report nine children with CM treated with orally administered ketoconazole and intraventricularly administered miconazole. Four of them had been treated initially with amphotericin B with resultant failure in one and severe toxicity in all four. The other five children were treated only with imidazoles. All nine children had evidence of ventriculitis at the time of diagnosis and had ventriculoperitoneal shunts inserted for control of increased intracranial pressure. There was no relapse or recrudescence of CM in a follow-up period of 32 to 90 months on imidazole therapy. The coccidioidal complement-fixation antibody titers in the cerebrospinal fluid of the lateral ventricle became negative in all children 3 to 51 months after diagnosis (mean, 17 months). The serum antibody titers demonstrated a 16- to 256-fold decrease from their maximal levels. Four children are still receiving intraventricular miconazole whereas the others have not received miconazole for an average of 51 months. Therapy with the imidazoles was well-tolerated. The main morbidity was related to the shunts required for control of increased intracranial pressure. There was no evidence of hepatic toxicity and no clinical evidence of adrenal insufficiency although transient adrenal suppression was demonstrated at 4 but not at 24 hours after ketoconazole administration.