Multi-azole resistance in Aspergillus fumigatus.
Azole resistance in Aspergillus spp. is unusual. We report a patient who received long-term treatment with itraconazole and voriconazole for bilateral chronic cavitary aspergillosis with aspergillomas whose isolates of Aspergillus fumigatus developed simultaneous resistance to itraconazole and voriconazole. A novel mutation (G138C) in the target gene (cyp51A) encoding 14alpha-demethylase was detected. The patient had some response to intravenous caspofungin, which he received six times weekly, without the development of resistance over 9 months.
Howard
Susan J
SJ
School of Medicine, The University of Manchester, Oxford Road, Manchester M13 9PL, UK. susan.j.howard@manchester.ac.uk
Webster
Ian
I
Moore
Caroline B
CB
Gardiner
Rebecca E
RE
Park
Steven
S
Perlin
David S
DS
Denning
David W
DW
D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use; D001228:Aspergillosis / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics; D000077336:Caspofungin; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D054714:Echinocandins; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology / Q000627:therapeutic use; D055666:Lipopeptides; D008172:Lung Diseases, Fungal / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use; D065819:Voriconazole
D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D011743:Pyrimidines; D013844:Thiazoles; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D000666:Amphotericin B; D003577:Cytochrome P-450 Enzyme System; C104066:ER 30346; C465526:cytochrome P-450 CYP51A, Aspergillus; D000077336:Caspofungin; D065819:Voriconazole