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.
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U2 - 10.1086/315643
DO - 10.1086/315643
M3 - Article
C2 - 10882607
AN - SCOPUS:0033943712
SN - 0022-1899
VL - 182
SP - 274
EP - 282
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -