Author/Editor		Howard, Susan J; Cerar, Daša; Anderson, Michael J; Albarrag, Ahmed; Fisher, Matthew C; Pasqualotto, Alessandro C; Laverdiere, Michel; Arendrup, Maiken C; Perlin, David S; Denning, Davis W
Title		Frequency and evolution of Azole resistance in Aspergillus fumigatus associated with treatment failure
Type		članek
Source		Emerg Infect Dis
Vol. and No.		Letnik 15, št. 7
Publication year		2009
Volume		str. 1068-76
Language		eng
Abstract		Azoles are the mainstay of oral therapy for aspergillosis. Azole resistance in Aspergillus has been reported infrequently. The first resistant isolate was detected in 1999 in Manchester, UK. In a clinical collection of 519 A. fumigatus isolates, the frequency of itraconazole resistance was 5%, a significant increase since 2004 (p<0.001). Of the 34 itraconazole-resistant isolates we studied, 65% (22) were cross-resistant to voriconazole and 74% (25) were cross-resistant to posaconazole. Thirteen of 14 evaluable patients in our study had prior azole exposure; 8 infections failed therapy (progressed), and 5 failed to improve (remained stable). Eighteen amino acid alterations were found in the target enzyme, Cyp51A, 4 of which were novel. A population genetic analysis of microsatellites showed the existence of resistant mutants that evolved from originally susceptible strains, different cyp51A mutations in the same strain, and microalterations in microsatellite repeat number. Azole resistance in A. fumigatus is an emerging problem and may develop during azole therapy.
Descriptors		ASPERGILLUS FUMIGATUS ASPERGILLOSIS AZOLES DRUG RESISTANCE, MICROBIAL MICROBIAL SENSITIVITY TESTS MICROSATELLITE REPEATS PHYLOGENY