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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.
Insights
Imidazole therapy, including ketoconazole and miconazole, shows promise for treating coccidioidal meningitis in young children. This approach offers improved efficacy and fewer side effects compared to Amphotericin B.
Area of Science:
- Mycology
- Pediatric Infectious Diseases
- Neuroscience
Background:
- Coccidioidal meningitis, a severe Coccidioides immitis infection, has a high mortality rate.
- Amphotericin B (AMB) is a standard treatment but carries significant toxicity, especially in young children.
- Limited data exists on AMB efficacy and safety in pediatric coccidioidal meningitis.
Purpose of the Study:
- To evaluate the efficacy and safety of imidazole-based therapy for coccidioidal meningitis in young children.
- To compare imidazole therapy with Amphotericin B in this patient population.
- To assess treatment outcomes in children with hydrocephalus and ventriculitis.
Main Methods:
- Retrospective analysis of six pediatric patients diagnosed with coccidioidal meningitis (19-74 months old).
- Treatment regimens included oral ketoconazole and intraventricular miconazole.
- Comparison of outcomes between initial AMB treatment and subsequent imidazole therapy.
Main Results:
- All six children showed clinical improvement with imidazole therapy (oral ketoconazole and intraventricular miconazole).
- Imidazole therapy was initiated in two patients, while four transitioned from AMB due to toxicity or failure.
- Major morbidities included shunt obstruction and bacterial superinfections, not directly related to imidazole efficacy.
Conclusions:
- Imidazole therapy (ketoconazole and miconazole) appears more effective and safer than AMB for pediatric coccidioidal meningitis.
- Imidazole therapy offers advantages of fewer side effects and avoids intrathecal/cisternal administration.
- Further research is warranted to confirm imidazole superiority in this vulnerable population.