Comparative In Vitro Activity of Amphotericine B, Itraconazole, Voriconazole and Posaconazole against Aspergillus fumigatus

Background. New azoles have been successfully used as treatment of invasive aspergillosis. The purpose of this study was to compare the in vitro activity of posaconazole (Posa) with that of amphotericin B (AmB), itraconazole (Itra) and voriconazole (Vor) against A. fumigatus isolates according to NCCLS method (M38-P), and to compare visual and spectrophotometric readings for MIC determination. Methods. A total of 106 A. fumigatus isolates were selected as follows: 88 clinical isolates from colonized patients, 18 from patients with invasive aspergillosis and 7 environmental isolates. Their in vitro susceptibility was evaluated by the NCCLS microdilution method (M38-P) in RPMI 1640 medium. Determination of results was made by visual and spectrophotometric readings (630 nm) after 48 hours incubation at 35 degreesC. Three A. fumigatus reference strains (IHEM 5734, 6149 and 13935) were included as control. Results. 1. Geometric mean MICs/MIC90 (microg/ml) obtained by visual reading were respectively 0.66/1 (AmB), 0.37/0.5 (Itra), 0.27/0.5 (Vor) and 0.02/0.03 (Posa). 2. MIC values were comparable by spectrophotometric and by visual readings for all antifungal agents tested (p>.05) and did not depend on the isolates origin (p>.05). 3. Posaconazole had the lowest MICs (p< 0.001). 4. The itraconazole-resistant reference strain did not give cross resistance with voriconazole and posaconazole. CONCLUSIONS: Among azoles, posaconazole had a better in vitro activity against A. fumigatus than did voriconazole or itraconazole. Spectrophotometric reading could replace the less standardized visual reading for NCCLS microdilution method and MIC values obtained were comparable among all A. fumigatus isolates.