Vol. 15, No. 7, July 2009 | Susan J. Howard, Dasa Cerar, Michael J. Anderson, Ahmed Albarrag, Matthew C. Fisher, Alessandro C. Pasqualotto, Michel Laverdiere, Maiken C. Arendrup, David S. Perlin, and David W. Denning
The study investigates the frequency and evolution of azole resistance in *Aspergillus fumigatus* associated with treatment failure. Azole resistance in *A. fumigatus* has been reported infrequently, with the first resistant isolate detected in 1999. In a clinical collection of 519 *A. fumigatus* isolates, the frequency of itraconazole resistance increased significantly since 2004 (from 1% to 8%, p<0.001). Of the 34 itraconazole-resistant isolates, 65% were cross-resistant to voriconazole, and 74% were cross-resistant to posaconazole. The study identified 18 amino acid alterations in the target enzyme, Cyp51A, including four novel mutations. Population genetic analysis of microsatellites showed that resistant mutants evolved from originally susceptible strains, with different *cyp51A* mutations in the same strain and microalterations in microsatellite repeat number. The findings highlight the emergence of azole resistance as a significant problem in *A. fumigatus* and the need for vigilance in identifying resistant strains, especially in immunocompromised patients.The study investigates the frequency and evolution of azole resistance in *Aspergillus fumigatus* associated with treatment failure. Azole resistance in *A. fumigatus* has been reported infrequently, with the first resistant isolate detected in 1999. In a clinical collection of 519 *A. fumigatus* isolates, the frequency of itraconazole resistance increased significantly since 2004 (from 1% to 8%, p<0.001). Of the 34 itraconazole-resistant isolates, 65% were cross-resistant to voriconazole, and 74% were cross-resistant to posaconazole. The study identified 18 amino acid alterations in the target enzyme, Cyp51A, including four novel mutations. Population genetic analysis of microsatellites showed that resistant mutants evolved from originally susceptible strains, with different *cyp51A* mutations in the same strain and microalterations in microsatellite repeat number. The findings highlight the emergence of azole resistance as a significant problem in *A. fumigatus* and the need for vigilance in identifying resistant strains, especially in immunocompromised patients.