High prevalence of azole-resistant Aspergillus fumigatus in adults with cystic fibrosis exposed to itraconazole

Aspergillus fumigatus is the most frequent fungus found in the sputum of cystic fibrosis (CF) subjects. Itraconazole is prescribed for allergic bronchopulmonary aspergillosis (ABPA) or Aspergillus bronchitis in CF subjects. We hypothesized that A. fumigatus isolates in the sputum of CF subjects with...

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Published in:Antimicrobial agents and chemotherapy Vol. 56; no. 2; p. 869
Main Authors: Burgel, Pierre-Régis, Baixench, Marie-Thérèse, Amsellem, Michaël, Audureau, Etienne, Chapron, Jeanne, Kanaan, Reem, Honoré, Isabelle, Dupouy-Camet, Jean, Dusser, Daniel, Klaassen, Corné H, Meis, Jacques F, Hubert, Dominique, Paugam, André
Format: Journal Article
Language:English
Published: United States 01.02.2012
Subjects:
Adult
Antifungal Agents - pharmacology
Aspergillosis, Allergic Bronchopulmonary - complications
Aspergillosis, Allergic Bronchopulmonary - drug therapy
Aspergillosis, Allergic Bronchopulmonary - epidemiology
Aspergillosis, Allergic Bronchopulmonary - microbiology
Aspergillus fumigatus - drug effects
Aspergillus fumigatus - genetics
Aspergillus fumigatus - isolation & purification
Azoles - pharmacology
Cohort Studies
Cystic Fibrosis - complications
Cystic Fibrosis - drug therapy
Cystic Fibrosis - epidemiology
Cystic Fibrosis - microbiology
Drug Resistance, Fungal
Female
Humans
Itraconazole - pharmacology
Itraconazole - therapeutic use
Male
Microbial Sensitivity Tests - methods
Prevalence
Sputum - microbiology
Young Adult
ISSN:1098-6596, 1098-6596
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Summary:Aspergillus fumigatus is the most frequent fungus found in the sputum of cystic fibrosis (CF) subjects. Itraconazole is prescribed for allergic bronchopulmonary aspergillosis (ABPA) or Aspergillus bronchitis in CF subjects. We hypothesized that A. fumigatus isolates in the sputum of CF subjects with previous exposure to itraconazole was associated with higher prevalence of azole resistance. From June 2010 to April 2011, sputum samples from adult CF subjects at Cochin University Hospital (France) were examined systematically for the detection of A. fumigatus. MICs of A. fumigatus isolates against azoles were screened using Etest, and reduced susceptibility to azoles was confirmed using the CLSI broth microdilution method. A. fumigatus was isolated from the sputum of 131/249 (52.6%) adult CF subjects, and 47/131 (35.9%) subjects had received previous treatment with itraconazole. Reduced A. fumigatus susceptibility to itraconazole (MIC, ≥2 mg/liter) was confirmed in 6/131 (4.6%) subjects. All 6 isolates also had reduced susceptibility to posaconazole (MIC, ≥0.5 mg/liter), and 3/6 isolates had reduced susceptibility to voriconazole (MIC, ≥2 mg/liter). Mutations in the cyp51A gene were detected at positions previously implicated to cause resistance in 5 isolates. Azole-resistant A. fumigatus isolates were found in 5/25 (20%) subjects exposed to itraconazole within the previous 3 years. High rates of azole-resistant A. fumigatus isolates were present in adult CF subjects and were associated with recent itraconazole exposure. Although the clinical implications of these findings will require further studies, the cautious use of itraconazole in adult CF subjects can be recommended.
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ISSN:1098-6596
1098-6596
DOI:10.1128/AAC.05077-11