TY - JOUR AU - Howard, Susan J. AU - Cerar, Dasa AU - Anderson, Michael J. AU - Albarrag, Ahmed AU - Fisher, Matthew C. AU - Pasqualotto, Alessandro C. AU - Laverdiere, Michel AU - Arendrup, Maiken C. AU - Perlin, David S. AU - Denning, David W. T1 - Frequency and Evolution of Azole Resistance in Aspergillus fumigatus Associated with Treatment Failure T2 - Emerging Infectious Disease journal PY - 2009 VL - 15 IS - 7 SP - 1068 SN - 1080-6059 AB - 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. KW - Aspergillus fumigatus KW - azoles KW - antifungal drug resistance KW - sterol 14-alpha demethylase CYP51A KW - Aspergillus KW - population genetics KW - microsatellites KW - research KW - United Kingdom DO - 10.3201/eid1507.090043 UR - https://wwwnc.cdc.gov/eid/article/15/7/09-0043_article ER - End of Reference