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Imidazole therapy of coccidioidal meningitis in children
Z M Shehab1, H Britton, J H Dunn
1Department of Pediatrics, Arizona Health Sciences Center, Tucson 85724.
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.
Insights
Imidazole antifungals, including ketoconazole and miconazole, offer a promising treatment for coccidioidal meningitis (CM) in children, reducing morbidity associated with traditional therapies.
Area of Science:
- Pediatric Infectious Diseases
- Mycology
- Neuroscience
Background:
- Coccidioidal meningitis (CM) poses significant morbidity in children despite reduced mortality from amphotericin B.
- Drug toxicity from amphotericin B contributes to morbidity in pediatric CM cases.
Purpose of the Study:
- To evaluate the efficacy and safety of imidazole antifungals (ketoconazole and miconazole) in treating pediatric coccidioidal meningitis.
- To assess imidazole therapy as an alternative to or in conjunction with amphotericin B for CM in children.
Main Methods:
- Nine children with CM, all exhibiting ventriculitis, were treated with oral ketoconazole and intraventricular miconazole.
- Four children had prior treatment with amphotericin B, experiencing failure or severe toxicity.
- Five children received imidazole therapy exclusively.
Main Results:
- No relapse or recrudescence of CM was observed during 32-90 months of follow-up with imidazole therapy.
- Cerebrospinal fluid coccidioidal antibody titers became negative in all patients; serum titers decreased significantly.
- Imidazole therapy was well-tolerated, with main morbidity linked to ventriculoperitoneal shunts, not drug toxicity.
Conclusions:
- Oral ketoconazole and intraventricular miconazole represent an effective and well-tolerated treatment strategy for pediatric coccidioidal meningitis.
- Imidazole antifungals can potentially mitigate the toxicity associated with amphotericin B in treating CM.
- Long-term imidazole therapy demonstrates sustained efficacy in achieving remission and serological cure in pediatric CM.