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. 2008 Jul;52(7):2468-72.
doi: 10.1128/AAC.00156-08. Epub 2008 May 12.

Epidemiological cutoffs and cross-resistance to azole drugs in Aspergillus fumigatus

Juan Luis Rodriguez-Tudela  1 , Laura Alcazar-Fuoli, Emilia Mellado, Ana Alastruey-Izquierdo, Araceli Monzon, Manuel Cuenca-Estrella
Affiliations

Epidemiological cutoffs and cross-resistance to azole drugs in Aspergillus fumigatus

Juan Luis Rodriguez-Tudela et al. Antimicrob Agents Chemother. 2008 Jul.

Abstract

Antifungal susceptibility testing of molds has been standardized in Europe and in the United States. Aspergillus fumigatus strains with resistance to azole drugs have recently been detected and the underlying molecular mechanisms of resistance characterized. Three hundred and ninety-three isolates, including 32 itraconazole-resistant strains, were used to define wild-type populations, epidemiological cutoffs, and cross-resistance between azole drugs. The epidemiological cutoff for itraconazole, voriconazole, and ravuconazole for the wild-type populations of A. fumigatus was < or =1 mg/liter. For posaconazole, the epidemiological cutoff was < or =0.25 mg/liter. Up till now, isolates susceptible to itraconazole have not yet displayed resistance to other azole drugs. Cross-resistance between azole drugs depends on specific mutations in cyp51A. Thus, a substitution of glycine in position 54 of Cyp51A confers cross-resistance between itraconazole and posaconazole. A substitution of methionine at position 220 or a duplication in tandem of a 34-bp fragment in the cyp51A promoter combined with a substitution of leucine at position 98 for histidine confers cross-resistance to all azole drugs tested. The results obtained in this study will help to develop clinical breakpoints for azole drugs and A. fumigatus.

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Figures

FIG. 1.
FIG. 1.
MIC distribution for itraconazole, voriconazole, ravuconazole, and posaconazole for all strains except those with an itraconazole MIC of ≥8 mg/liter.
See this image and copyright information in PMC

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