Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system

Andreas H. Groll, Neelam Giri, Vidmantas Petraitis, Ruta Petraitiene, Myrna Candelario, John S. Bacher, Stephen C. Piscitelli, Thomas J. Walsh

Research output: Contribution to journalArticle

Abstract

The central nervous system (CNS) distribution and antifungal efficacy of all 4 approved formulations of amphotericin B (AmB) were investigated in a rabbit model of hematogenous Candida albicans meningoencephalitis. Treatment with AmB deoxycholate (1 mg/kg/day) or liposomal AmB (5 mg/kg/day) yielded the highest peak plasma concentration (C(max)), area under concentration versus time curve from zero to 24 h (AUC0-24), and time during dosing level τ (T(τ)) > minimum inhibitory complex (MIC) values and led to complete eradication of C. albicans from brain tissue (P < .05 vs. untreated controls). By comparison, AmB colloidal dispersion and AmB lipid complex (5 mg/kg/day each) were only partially effective (not significant vs. untreated controls). There was a strong correlation of C(max), AUC0-24, C(max)/MIC, AUC0-24/MIC, and T(τ) > MIC with clearance of C. albicans from brain tissue (P ≤ .0002). Although pharmacodynamic parameters derived from the MIC of free AmB were highly predictive of antifungal efficacy, parameters derived from MICs of individual formulations were not predictive. AmB deoxycholate and liposomal AmB had the greatest antifungal efficacy. This activity was concentration and time dependent.

Original languageEnglish (US)
Pages (from-to)274-282
Number of pages9
JournalJournal of Infectious Diseases
Volume182
Issue number1
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Groll, A. H., Giri, N., Petraitis, V., Petraitiene, R., Candelario, M., Bacher, J. S., Piscitelli, S. C., & Walsh, T. J. (2000). Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system. Journal of Infectious Diseases, 182(1), 274-282. https://doi.org/10.1086/315643