Seufert, R., Sedlacek, L., Kahl, B., Hogardt, M., Hamprecht, A., Haase, G., Gunzer, F., Haas, A., Grauling-Halama, S., MacKenzie, C. R., Essig, A., Stehling, F., Sutharsan, S., Dittmer, S., Killengray, D., Schmidt, D., Eskandarian, N., Steinmann, E., Buer, J., Hagen, F., Meis, J. F., Rath, P. -M. and Steinmann, J. (2018). Prevalence and characterization of azole-resistant Aspergillus fumigatus in patients with cystic fibrosis: a prospective multicentre study in Germany. J. Antimicrob. Chemother., 73 (8). S. 2047 - 2054. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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Abstract

Objectives: Aspergillus fumigatus is the most prevalent filamentous fungus in the respiratory tract of patients with cystic fibrosis (CF). The aim of this prospective multicentre study was to investigate the prevalence of azole-resistant A. fumigatus (ARAF) in respiratory secretions from CF patients across Germany and to characterize ARAF isolates by phenotypic and molecular methods. Methods: Twelve tertiary care centres from Germany participated in the study. In total, 2888 A. fumigatus isolates from 961 CF patients were screened for ARAF by using azole-containing agar plates. Antifungal susceptibility testing of isolates was performed by broth microdilution according to EUCAST guidelines. Analysis of mutations mediating resistance was performed using PCR and sequencing of the cyp51A gene. Furthermore, genotyping by microsatellite PCR was performed. Results: Of a total of 2888 A. fumigatus isolates, 101 isolates from 51 CF patients were found to be azole resistant (prevalence per patient 5.3%). The Essen centre had the highest prevalence (9.1%) followed by Munich (7.8%), Munster (6.0%) and Hannover (5.2%). Most ARAF isolates (n = 89) carried the TR34/L98H mutation followed by eight G54E/R, one TR46/Y121F/T289A and one F219S mutation. In two isolates no mutation was found. Genotyping results showed no major clustering. Forty-five percent of CF patients with ARAF had previously received azole therapy. Conclusions: This is the first multicentre study analysing the prevalence of ARAF isolates in German CF patients. Because of a resistance rate of up to 9%, susceptibility testing of A. fumigatus isolates from CF patients receiving antifungal treatment should be part of standard diagnostic work-up.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Seufert, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sedlacek, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kahl, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hogardt, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamprecht, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haase, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gunzer, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haas, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grauling-Halama, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
MacKenzie, C. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Essig, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stehling, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sutharsan, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dittmer, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Killengray, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eskandarian, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinmann, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buer, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hagen, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meis, J. F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rath, P. -M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinmann, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-178254
DOI: 10.1093/jac/dky147
Journal or Publication Title: J. Antimicrob. Chemother.
Volume: 73
Number: 8
Page Range: S. 2047 - 2054
Date: 2018
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2091
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TRANSPLANT RECIPIENTS; TRIAZOLE RESISTANCE; SUSCEPTIBILITY; ITRACONAZOLE; MANAGEMENT; MUTATION; TR/L98HMultiple languages
Infectious Diseases; Microbiology; Pharmacology & PharmacyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17825

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