Azole antifungal resistance in Aspergillus fumigatus: 2008 and 2009.
OBJECTIVE
Resistance to azole antifungal drugs in Aspergillus fumigatus is now a major clinical problem in some locations. Here we update our previous experience with data from 2008-09.


METHODS
We tested all A. fumigatus isolates submitted to the Mycology Reference Centre Manchester in 2008 and 2009 for susceptibility to itraconazole, voriconazole and posaconazole. We undertook CYP51A sequencing for most of the azole-resistant isolates.


RESULTS
Of 230 isolates, 64 (28%) were azole resistant. In 2008 and 2009, 14% and 20% of patients had resistant isolates, respectively. During this period 62 of 64 (97%) were itraconazole resistant, 2 of 64 (3%) were only voriconazole resistant and 78% of cases were multi-azole resistant. Forty-three percent of isolates did not carry a cyp51A mutation (previously the most common azole resistance mechanism), indicating that other mechanisms must be responsible and are increasing in frequency.


CONCLUSIONS
Azole resistance is evolving and growing in frequency. Established and novel mechanisms may be responsible.
Bueid
Ahmed
A
The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Howard
Susan J
SJ
Moore
Caroline B
CB
Richardson
Malcolm D
MD
Harrison
Elizabeth
E
Bowyer
Paul
P
Denning
David W
DW
D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000302:isolation & purification; D001393:Azoles / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D014230:Triazoles / Q000494:pharmacology; D065819:Voriconazole
D000935:Antifungal Agents; D001393:Azoles; D004271:DNA, Fungal; D005656:Fungal Proteins; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus; D065819:Voriconazole