High Loading Doses of Liposomal Amphotericin B (L-Ab) in the Treatment of Experimental Pulmonary Aspergillosis

J. GAVALDà, P. Lí“PEZ, M. T. MARTíN, X. GOMIS, J. L. RAMíREZ, A. PAHISSA

Author address: 

Hospital Vall d'Hebron, Barcelona, Spain.

Abstract: 

The efficacy of treatment of invasive aspergillosis remains suboptimal. We have previously demonstrated that L-Ab at 10 mg/kg/d was more effective than amphotericin B deoxycholate (AB) in the treatment of EPA. It has also been shown that increasing L-Ab doses lead to an augment of Ab concentration in lung or kidney tissue -but not in liver-, suggesting a saturable mechanism that involves reticuloendothelial system uptake. Aim: To evaluate the efficacy of L-Ab at a loading dose of 10 mg/kg/d followed by 3 mg/kg/d in a model of EPA. Methods: Wistar rats were treated thrice weekly with cortisone acetate 125 mg/kg throughout the experiment and transtracheally infected on day 15th with 0.3 mL of 1x107 spores/mL of a clinical isolate of Aspergillus fumigatus. The treatment, administered through an iv catheter, started 24 h later. Groups of treatment: control (n=28); AB 1 mg/kg/d 7 d (n=22); L-Ab 5 mg/kg/d 7 d (n=32) or L-Ab 10 mg/kg for 2 (n=33), 3 (n=34) or 4 (n=21) d followed by L-Ab 3 mg/kg/d until day 7. Efficacy was evaluated in rats treated ³ 5 d by chitin quantification as indicative of fungal biomass in lungs; lung weight and survival data were recorded. Chitin was extracted by the action of alkali depolymerized to glucosamine and assayed colorimetrically. Result are given as mean (95% IC) mg glucosamine/paired lungs. Mann-Witney U Wilcoxon; Kaplan-Meier-Log rank test as statistics (survival). Results: 78.6% of control rats died before day 8. All treatment regimens significantly increased survival compared with control group, and significantly decreased lung weight. Only L-Ab 10 mg/kg for 4 d followed by 3 mg/kg significantly increased survival (76.2 vs 45.4%) and reduced the weight of the lungs (1.6 g vs 2.1 g p<.05 and="" the="" chitin="" content="" in="" lung="" vs="" p="" compared="" with="" ab.="" conclusion:="" treatment="" of="" invasive="" aspergillosis="" may="" be="" improved="" by="" using="" loading="" doses="" mg="" liposomal="" amphotericin="" b.="">
2002

abstract No: 

M-1817

Full conference title: 

42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 42nd