Emergence in vivo of Aspergillus terreus with reduced azole susceptibility and a CYP51A M220I alteration in a cystic fibrosis patient

M.C. Arendrup*, R.H. Jensen, K. Grif, H.K. Johansen, M. Skov, T. Pressler, K.L. Mortensen, C. Lass-Flo¨rl

Author address: 

(Copenhagen, DK; Innsbruck, AT)

Abstract: 

Objectives: Aspergilli are frequently found in the airways of CF patients. A. fumigatus is the predominant species and 4.5% of these have recently been shown to be azole resistant in a Danish cohort. Azole resistance in A. terreus is rarely reported but of clinical significance due to this species being intrinsically resistant to amphotericin B. We here report the emergence of A. terreus isolates with reduced azole susceptibility and investigate the underlying mechanism and origin. Methods: Twenty sequential A. terreus isolates from a single CF patient (MB) obtained over a 7.5 year period and six unrelated A. terreus isolates were included. Susceptibility testing was performed (EUCAST EDef 9.1 methodoly). Breakpoints have not yet been established but A. terreus isolates with itraconazole (ITR) MIC ≤0.5 mg/L were regarded as susceptible based on MIC ranges for wild type isolates. The CYP51A gene and promoter was sequenced (primers designed based on the reference strain NIH2624 ATEG05917). The isolates genotyped using RAPD-PCR and five different primers for maximal discriminatory power: A-ter2 (5-GCTGGTGG-3), NS7 (5-GAGGCAATAACAGGTCTGTGATGC-3), (R108 (5-GTATTGCC CT-3), CII (5-GCGCACGG-3) and P4 (5-GATAGATAGATAGAT-3). Results: Susceptibility testing of the isolates from MB identified five isolates as ITR S (MICs 0.250.5 mg/L): 2/2 from 2003 to 4, 2/7 from 2007 and 1/9 isolates from 2009. ITR MICs for the remaining 15 isolates were 14 mg/L. In contrast the ITR MICs of the six control isolates were 0.060.125 mg/L. Voriconazole (VOR) MICs were 1 4 mg/L for the MB isolates but 0.250.5 mg/L for the control isolates. The posaconazole (PSC) MICs were 0.060.5 mg/L for the MB isolates and
2012

abstract No: 

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Full conference title: 

22nd European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 22nd (2012)