Efficacy of Nebulized Liposomal Amphotericin B (N-LAb) in the Treatment of Experimental Pulmonary Aspergillosis (EPA).

J. GAVALDA, P. LOPEZ, M. MARTIN, X. GOMIS, J. RAMIREZ, O. LEN, D. RODRIGUEZ, Y. PUIGFEL, I. RUIZ, A. PAHISSA

Author address: 

Hospital Vall d'Hebron, Barcelona, Spain.

Abstract: 

Background: It has been demonstrated that increasing L-Ab i.v., doses lead to an augment of amphotericin concentration in lung and increase efficacy in animal models. Studies in rats demonstrated that liposomal amphotericin B nebulization allows a deposition in the lung tissue with an increase of local concentration. Aim: To evaluate the efficacy of nebulized LAb in the treatment of in a model of EPA Methods: Wistar rats treated thrice weekly with cortisone acetate 125 mg/kg and feeded with low protein diet 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, and/or exposition in chamber to an aerosol provided by nebulization (CR60 nebulizator) of 2 mg/kg of LAb or 1 mg/kg of Ab deoxycolate (AB), started 24 h after the infection for 10 d. Groups of treatment: control (n=23); AB 1 mg/kg/d IV (n=25); L-Ab 5 mg/kg/d IV (n=27); N-LAb 2 mg/kg/d (n=16); N-LAb 2 mg/kg/d + LAb 5 mg/kg/d IV (n=16); Nebulized AB (NAB) 1 mg/kg/d (n=18). Survival data were recorded during treatment. Efficacy was evaluated in rats treated > 5 d by lung weight and chitin quantification as indicative of fungal biomass in lungs. Results are given as mean (95% IC) mg glucosamine/paired lungs. ANOVA analysis; Kaplan-Meier-Log rank test as statistics (survival). Results: All treatment regimens significantly increased survival compared with control group (p<.05 only="" both="" treatments="" with="" n-lab="" and="" increased="" survival="" vs="" ab="" iv="" lab="" reduced="" the="" weight="" chitin="" content="" in="" lung="" g="" ug="" respectively="" compared="" conclusions:="" efficacy="" of="" epa="" treatment="" is="" improved="" administering="" nebulized="" liposomal="" amphotericin="" b="" ab.="" this="" strategy="" may="" be="" a="" complementary="" that="" prognosis="" disease="" humans.="">
2003

abstract No: 

M-356

Full conference title: 

43rd Interscience Conference on Antimicrobial Agents
    • ICAAC 43rd