Efficacy of high loading doses of liposomal amphotericin B (L-Ab) in the treatment of experimental pulmonary aspergillosis (EPA)

J Gavalcil, P Lopez, MT Martin, X Gomis, JL Ramirez, I Ruiz, C Pigrau, B Almirante, A Pahissa.

Abstract: 

The efficacy of antifungal treatment remains suboptimal in patients with invasive pulmonary aspergillosis. 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 dosage leads to an increment of amphotericin B concentration in reticulo-endothelial system (RES) organs, sugesting a saturable mechanism that involves RES uptake. The aim of this study was the evaluation of 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 twice weekly with cortisone acetate 125 mg/kg throughout the experiment and transtracheally infected on day 15th with 0.3 mL of 1 x 107 conidia/mL of a clinical Aspergillis fumigatus isolate. The treatment, administered trough an i.v catheter, started 24h later Groups of treatment Control (n=28), Ab 1 mg/kg/d 7 d (n=22), L-Ab 5rng/kg/d 7 d (n=32), or L-Ab 10 mg/k for 2 (n=33),3(n=34) or 4 d (n=21) followed by L-Ab 3 mg/kg/d until day 7 of treatment. Efficacy was evaluated in rats treated -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 alkaly, depolymerised to glucosamine and assayed colorimetrically. Result are given as mean (95%1C) mg glucosaminelpaired lungs. Statistics: ANOVA analysis, Kaplan-Meyer, logrank test (survival). Results: 78.6% of control rats died before day 8. All treatment regimens significantly increased the survival compared to control group. Only L-Ab 10 mg/kg 4d followed by 3 mg/kg/d significantly increased survival (76.2 vs 45.4%) and reduced the chitin content in lungs compared to AB (P
2001

abstract No: 

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Full conference title: 

Trends in Invasive fungal Infections 6, 2001
    • TIFI 6th