In vitro survey of triazole cross-resistance among more than 700 clinical isolates of Aspergillus species

Few data exist to describe in vitro patterns of cross-resistance among large collections of clinical Aspergillus isolates, including those of species other than Aspergillus fumigatus. We examined 771 Aspergillus spp. clinical isolates collected from 2000 to 2006 as part of a global antifungal surveillance program ( 553 A. fumigatus, 76 A. flavus, 59 A. niger, 35 A. terreus, and 24 A. versicolor isolates and 24 isolates of other Aspergillus species). Antifungal susceptibility testing was performed by the Clinical and Laboratory Standards Institute ( CLSI) M38-A broth dilution method with itraconazole ( ITR), posaconazole ( POS), ravuconazole ( RAV), and voriconazole ( VOR). We examined the potential for cross-resistance by using measures of correlation overall and by species. For most Aspergillus isolates ( from 88% of isolates for ITR to 98% of isolates for VOR and POS), MICs of each triazole were <= 1 mu g/ml. When all 771 isolates were examined, there were statistically significant correlations for all six triazole-triazole pairs. For A. fumigatus, the strongest correlations seen were those between VOR and RAV MICs ( r = 0.7) and ITR and POS MICs ( r = 0.4). Similarly, for A. flavus, only VOR and RAV MICs and ITR and POS MICs demonstrated statistically significant positive correlations. We have demonstrated correlations among triazole MICs for Aspergillus, which for the most common species ( A. fumigatus and A. flavus) were strongest between VOR and RAV MICs and ITR and POS MICs. However, Aspergillus species for which MICs of VOR or POS were > 2 mu g/ml remain extremely rare (< 1% of isolates).