Evaluation of the In vitro Potency of Itraconazole , Voriconazole , and Posaconazole and Resistance in Aspergillus Isolates from the United States

Ref ID: 19567


NP Wiederhold1*, AW Fothergill1, DI McCarthy1, C Sanders1, DA Sutton1

Author address:

1Pathology, UTHSCSA, San Antonio, USA

Full conference title:

6th Advances Against Aspergillosis 2014


The triazoles itraconazole, voriconazole, and posaconazole are important agents for the treatment of
infections caused by Aspergillus species. However, increased resistance to these agents in Aspergillus
fumigatus isolates has been reported in some areas of the world, including many parts of Europe.
Our objective was to evaluate the in vitro potency of itraconazole, voriconazole, and posaconazole
against common Aspergillus species, and determine the rates of resistance to these agents in isolates
collected from institutions in the United States.
The antifungal susceptibility database in the Fungus Testing Laboratory at the UT Health Science
Center San Antonio was queried for itraconazole, voriconazole, and posaconazole MIC data against
A. fumigatus, A. terreus, A. flavus, and A. niger isolates from 2001 through 2013. This database is
populated with antifungal MIC data against fungal isolates sent to our mycology reference laboratory
from institutions across the U.S. Susceptibility testing was performed according to CLSI guidelines.
The MIC50, MIC90, and geometric mean (GM) MIC values were determined. Differences in
GM MIC values were assessed for significance by ANOVA with Tukey’s post-test for multiple
comparisons. Isolates were also classified as resistant based on proposed clinical breakpoints
(voriconazole & itraconazole > 4 μg/ml, posaconazole > 1 μg/ml; Verweij et al. Drug Resist Update
2009). Differences in the number of isolates classified as resistant were assessed for significance
using Fisher’s exact test.
Posaconazole had the most potent activity of each of the triazoles tested. The GM MIC values
of this agent (range 0.131 – 0.313 μg/ml; p < 0.0001) were significantly lower than those of itraconazole (0.232 - 0.979 μg/ml) and voriconazole (0.471 - 0.801 μg/ml) against each of the four species evaluated. Similarly, itraconazole was significantly more potent than voriconazole against A. fumigatus, A. terreus, and A. flavus. In contrast, voriconazole was more potent than itraconazole against A. niger isolates. Azole resistance was highest in A. fumigatus against each agent (range 2.58% - 4.06%) and for itraconazole and posaconazole against A. niger isolates (6.87% and 5.46%, respectively). In A. fumigatus there was a trend towards increased voriconazole resistance in isolates tested from 2007 to 2013 compared to the earlier period of 2001 to 2006 (4.23% vs. 2.42%; p = 0.0721). In 425 A. fumigatus isolates for which MIC values were available for each agent, resistance was observed in 7.06% with 2.35% of isolates demonstrating resistance to all three triazoles. Conclusions: Each of the triazoles demonstrated in vitro activity against Aspergillus, with posaconazole being the most potent agent against each species. Resistance was observed for each agent against in A. fumigatus and for itraconazole and posaconazole in A. niger. In addition, there was a trend towards increased voriconazole resistance in A. fumigatus over time. Further surveillance studies are needed to monitor for triazole resistance in Aspergillus species in the U.S.

Abstract Number: 93

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

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