First report of azole-resistance from clinical Aspergillus fumigatus isolates in the Middle East

Ref ID: 19191

Author:

S. Seyedmousavi, S.J. Hashemi, J. Zoll, M.T. Hedayati, J.W. Mouton, W.J.G. Melchers, P.E. Verweij

Author address:

Nijmegen, NL; Tehran, IR; Sari, IR

Full conference title:

23rd European Congress of Clinical Microbiology and
Infectious Diseases

Date: 27 April 2014

Abstract:

Objectives: Aspergillus fumigatus is a major cause of allergic syndromes, aspergilloma and life threatening invasive infections in immunocompromised hosts. To date, a wide range of mutations in A. fumigatus have been described conferring azole-resistance, which commonly involves modifications in the cyp51A-gene (substitutions at codons G54, G138, P216, F219, M220, G448 and specifically codon L98 in combination with a 34-bp tandem repeat in the promoter region of the gene) , the target for azole antifungals. We investigated the prevalence and spread of azole-resistance in clinical A.fumigatus isolates stored over a 6-year period (2003-2009) at Tehran University Mycology Reference Centre in Iran.
Methods: 124 clinical A. fumigatus isolates obtained from patients underlying invasive pulmonary aspergillosis, chronic obstructive pulmonary disease, allergic bronchopulmonary aspergillosis and aspergilloma, were investigated for the antifungal activity of itraconazole, voriconazole, posaconazole and amphotericin B using a broth microdilution test, according to EUCAST reference method. For the isolates with azole-resistance phenotype, the cyp51A-gene and its promoter was amplified and sequenced for the detection of mutations leading to triazole resistance. From all azole-resistant isolates as well as three controls, six microsatellite loci (STR Af 3A, 3B, 3C, 4A, 4B, and 4C) were amplified to determine the genetic relatedness between the isolates, and compared to a set of 20 Dutch TR34/L98H-positive isolates.
Results: Of the 124 A. fumigatus isolates tested, 4 (3.2%) had high MIC values of itraconazole (>16 mg/L) and voriconazole (4 mg/L). Sequence analysis of the cyp51A-gene showed the TR34/L98H genotype in three isolates. Two of the azole-resistant isolates showed identical patterns by microsatellite typing, although all tested isolates were different from the 20 Dutch TR34/L98H controls.
Conclusion: We report for the first time from Middle East the isolation of azole-resistant A.fumigatus harboring the TR34/L98H resistance mechanism. Azole resistance, especially the TR34/L98H resistance mechanism is wide-spread and international surveillance is warranted.

Abstract Number: P990

Conference Year: 2013

Link to conference website: http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=164630&XNSPRACHE_ID=2&XNKONGRESS_ID=180&XNMASK

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