Frequency and Evolution of Azole Resistance in Aspergillus fumigatus Associated with Treatment Failure1

Howard, Susan J.; Cerar, Dasa; Anderson, Michael J.; Albarrag, Ahmed; Fisher, Matthew C.; Pasqualotto, Alessandro C.; Laverdiere, Michel; Arendrup, Maiken C.; Perlin, David S.; Denning, David W.

i

Frequency and Evolution of Azole Resistance in Aspergillus fumigatus Associated with Treatment Failure1

Supporting Files Public Domain

Jul 2009
By Howard, Susan J. ; Cerar, Dasa ; Anderson, Michael J.

Details

Alternative Title:

Emerg Infect Dis
Personal Author:

Howard, Susan J. ; Cerar, Dasa ; Anderson, Michael J. ; Albarrag, Ahmed ; Fisher, Matthew C. ; Pasqualotto, Alessandro C. ; Laverdiere, Michel ; Arendrup, Maiken C. ; Perlin, David S. ; Denning, David W.
Description:

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.
Subjects:
Source:

Emerg Infect Dis. 15(7):1068-1076.
Document Type:

Journal Article
Volume:

15
Issue:

7
Download URL:

https://stacks.cdc.gov/view/cdc/17512/cdc_17512_DS1.pdf
File Type:

[PDF - 655.31 KB]
Collection(s):

Emerging Infectious Diseases
Main Document Checksum:

urn:sha256:2e377978c9e653933307113d365ce99e94f0c8873ae7d19e67ffa7217e72a627

ON THIS PAGE

Details Supporting Files

Was this page helpful?

Found an issue?

Send us an email at:

publishinghd@cdc.gov

CDC STACKS serves as an archival repository of CDC-published products including scientific findings, journal articles, guidelines, recommendations, or other public health information authored or co-authored by CDC or funded partners.

As a repository, CDC STACKS retains documents in their original published format to ensure public access to scientific information.