Resistance to Voriconazole Due to a G448S Substitution in Aspergillus fumigatus in a Patient with Cerebral Aspergillosis

Abstract

A voriconazole-resistant isolate of Aspergillus fumigatus was recovered from an immunocompetent patient receiving long-term antifungal therapy for cerebral aspergillosis. A G448S amino acid substitution in the azole target (Cyp51A) was identified as the cause of the resistance phenotype. This article describes the first isolation of a voriconazole-resistant A. fumigatus isolate from an immunocompetent patient in Spain. CASE REPORT

Candida tropicalis Antifungal Cross-Resistance Is Related to Different Azole Target (Erg11p) Modifications

“…The effects of Erg11p mutations at G464 and Y132 on azole susceptibility have been reported previously in different yeasts and filamentous fungi (59)(60)(61)(62)(63). The Y132H and G464S modifications conferred azole resistance on C. albicans (59).…”

Is Azole Resistance in Aspergillus fumigatus a Problem in Spain?

“…The isolates from the remaining patient showed a mutation in the cyp51A gene, thus demonstrating the presence of resistance. The patient had been living in another city and was transferred to our hospital to be treated for IA in 2011 (48), suggesting that resistance to azoles in A. fumigatus isolates collected in our hospital is minimal (0.7% of patients infected by this species).…”

On the evolution of azole resistance in Aspergillus fumigatus

“…This results in ergosterol depletion and accumulation of toxic sterols (Joseph-Horne and Hollomon 1997). The most common resistance mechanism known includes the alteration of the cyp51A gene (Howard et al 2006;Howard et al 2009;Bueid et al 2010;van der Linden et al 2011(Mellado et al 2007Mavridou et al 2010;Snelders et al 2010;Chowdhary et al 2012b;Pelaez et al 2012;Rath et al 2012;Rocchi et al 2014a;Wiederhold et al 2015)). In the last decade, widespread resistance emerged against itraconazole, and more recently to voriconazole, and numerous resistant strains have been isolated from patients.…”