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

TY - JOUR

T1 - Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system

AU - Groll, Andreas H.

AU - Giri, Neelam

AU - Petraitis, Vidmantas

AU - Petraitiene, Ruta

AU - Candelario, Myrna

AU - Bacher, John S.

AU - Piscitelli, Stephen C.

AU - Walsh, Thomas J.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0033943712

U2 - 10.1086/315643

DO - 10.1086/315643

M3 - Article

C2 - 10882607

SN - 0022-1899

VL - 182

SP - 274

EP - 282

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 1

ER -