ltraconazole resistance of Aspergillus spp. In a murine model of disseminated aspergillosis

E. Dannaoui, E. Borel, E Persat, E Symoens, S. Picot, M.A. Piens, R. Grillot, M Perraud , M.F. Monier, F Chapuis, B Lebeau, J Burnod, N Nolard, F Symoens, K Goens, S Heinemann, J.M. Bastide, M Mallie, D Castel, S Berthou, F Penaud, T De Meeus, M.A.


Objectives: To evaluate in a murine model of aspergillosis the in vivo efficacy of itraconazole (ITZ) against different Aspergillus spp. isolates.Methods: A murine model of disseminated aspergillosis was used. Mice were infected intravenously with a calibrated spore suspension. Preliminary studies were performed to determine the LD90 for each strain. ITZ was administered for 10 consecutive days starting 2 h after infection. Drug efficacy was assessed by determining delay in mortality and organ burdens. Two A. fumigatus isolates were tested: IHEM 9900 susceptible to ITZ in vitro (SITZ) and AF 1422 resistant to ITZ in vitro (RITZ). Two referenced ITZ-resistant strains (Denning et al, J Antimicrob Chemother 1997; 40: 401-14) were used as controls. ITZ-susceptible and -resistant A. terreus isolates were also tested.Results. In vitro susceptibility and in vivo outcome for reference strains were similar to those previously published. IHEM 9900 (SITZ) was susceptible in vivo and for AF 1422 (RITZ) the in vitro resistance was confirmed in vivo. Similar results were obtained for A. terreus isolates, with a correlation between in vitro resistance and in vivo outcome.Conclusions: We showed that the resistance of Aspergillus spp. to ITZ could be detected in vitro and could be confirmed in vivo in a murine model of disseminated aspergillosis. These results suggest that in vitro susceptibility testing of clinical Aspergillus isolates is appropriate.

abstract No: 


Full conference title: 

9th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 9th (1999)