Azole cross resistance in Aspergillus fumigatus

J.Mosquera, P.Warn, C.Moore, D.Denning


Background: Itraconazole (ITZ) is currently the only oral treatment for the human pathogen Aspergillus, but new azoles are currently being studied. Standardization of azole in-vitro susceptibility testing is in process. No study has presented consistent azole cross resistance results for more than a few Aspergillus strains. Objectives: To study azole cross resistance in Aspergillus fumigatus. Methods: 15 A fumigatus strains, obtained from different patients and with ITZ susceptibilities ranging from 0.12 to >8 mg/mL (14 higher than 0.25 mg/mL and 10 of these higher than 1 mg/mL), were tested in-vitro against ITZ, Ravuconazole/BMS-207147 (RCZ), Posaconazole/SCH 56592 (PCZ) and Voriconazole (VCZ). A validated microtire method which is able to detect ITZ resistance in Aspergillus fumigatus (Denning et al. 1997. J. Antimicrobial Chemother 40: 401) was employed. Conditions were: RPMI-1640 + 2% glucose medium, inoculum counted in a haemocytometer, final inoculum size of 5x 105 CFU/mL and microdilution plates incubated at 37 °C for 46-50 h, read visually with a 100% inhibition of growth endpoint. The highest and lowest final inocula of the range proposed in the NCCLS M-38P document (0.4x 104 and 5x 104 CFU/mL) were also compared, in order to analyze the effect of the inoculum.

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11th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 11th (2001)