Journal Article

In vitro interactions between amphotericin B and hydrocortisone: potential implications for intrathecal therapy

Greg Hodge, Stuart H. Cohen and George R. Thompson

in Medical Mycology

Published on behalf of International Society for Human and Animal Mycology

Volume 53, issue 7, pages 749-753
Published in print September 2015 | ISSN: 1369-3786
Published online July 2015 | e-ISSN: 1460-2709 | DOI: https://dx.doi.org/10.1093/mmy/myv047
In vitro interactions between amphotericin B and hydrocortisone: potential implications for intrathecal therapy

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  • Infectious Diseases
  • Medical Toxicology
  • Environmental Science
  • Mycology and Fungi
  • Veterinary Medicine

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Fungal meningitis remains a severe and often lethal infection requiring aggressive antifungal therapy and in refractory cases the use of intrathecal amphotericin B (AmB). Administration of amphotericin B by this method may result in clinically apparent adverse reactions such as paresthesias, radiculitis, or myelopathy. Coadministration of hydrocortisone is therefore often given in an attempt to avoid these effects; however, the potential consequences of this approach on fungal growth or on drug synergy/antagonism had not previously been assessed. We used the checkerboard titration broth microdilution method to analyze interactions by fractional inhibitory concentration indices (FICIs). The combination of amphotericin B and hydrocortisone resulted in synergy or indifference against all isolates (Candida, Cryptococcus, and Coccidioides) during in vitro testing at low concentrations. Antagonism was observed using higher hydrocortisone concentrations (those not observed in vivo) suggesting possible steric hindrance or binding to AmB may occur at doses unlikely to be present during clinical care. Concurrent hydrocortisone and AmB administration should not be avoided due to in vitro antagonism concerns.

Keywords: Coccidioides; coccidioidomycosis; meningitis; refractory; amphotericin B; hydrocortisone; intrathecal therapy; Candida; Cryptococcus

Journal Article.  2315 words.  Illustrated.

Subjects: Infectious Diseases ; Medical Toxicology ; Environmental Science ; Mycology and Fungi ; Veterinary Medicine

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