Prophylactic Efficacy of Liposomal Amphotericin B (LAmB) in a New Murine Model of Recurrent Pulmonary Aspergillosis Following Airborne Exposure to Aspregillus fumigatus in Immunosuppressed Mice

Ref ID: 18657

Author:

C. Leleu, Other – PhD Student, J. Menotti, PharmD, PhD – PharmD, PhD, P. Meneceur – Engineer, A. Sulahian, PhD – PhD, F. Derouin, MD, PhD – MD, PhD;

Author address:

Univ. Paris Diderot, Paris, France.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Invasive aspergillosis (IA) in immunosuppressed (IS) hosts is believed to be directly consecutive to inhalation of spores or to an immunosuppression-induced reactivation of a previously acquired non-invasive Aspergillus infection. In order to study the efficacy of antifungal drug to prevent recurrent aspergillosis, we developed an in vivo model of recurrent pulmonary IA and then assessed the prophylactic activity of LAmB (AmBisome, Gilead) in this model. Methods: In each experiment, 30-40 Balb/c mice were used; 17-25 were exposed for 60 min to an aerosol of spores of A. fumigatus at a concentration of 1.5±2.103 spores/L. At day 10 (d10), d17 and d24 after exposure, all mice except exposure control mice (EC) were immunosuppressed with cyclosporine and corticoid. One group of IS mice was treated with LAmB, 15 mg/kg, given i.p. at d10 and a second group was untreated. Quantitative cultures of the lungs of infected mice and galactomannan levels in lung homogenates were determined at d3, 5, 10, 14, 21 and d28 in EC mice and at d21 and d28 in IS mice. Results: All EC mice had positive lung cultures at d3 and d5 (30 – 650 cfu/g). Fungal burdens decreased from d5 to reach undetectable or low levels at d10 and remained negative in all mice at d28. In IS mice not receiving LAmB, lung cultures were positive in 20% of mice at d21 and 100% of mice at d28 (2 experiments) with high fungal burdens comprised between 20 and >1000 cfu/g at d28. In mice treated with LAmB the recurrence rate was reduced by 56% compared to untreated mice (Fisher test, p=0.034) with lower fungal burdens during recurrences compared to those of untreated mice (Mann-Whitney, p=0.007) Conclusion: A high rate of reactivation after airborne exposure to A. fumigatus spores followed by immunosuppression was obtained, providing a relevant model to study drug prevention of recurrent IA. Prophylactic administration of LAmB was found to significantly reduce the reactivation rate and fungal burdens compared to untreated controls.

Abstract Number: M-397

Conference Year: 2012

Link to conference website: NULL

New link: NULL

Conference abstracts, posters & presentations

Showing 10 posts of 17325 posts found.

  • Title

    Author

    Year

    Number

    Poster