Paradoxal Trends in Azole-Resistant Aspergillus fumigatus in a National Multicenter Surveillance Program, the Netherlands, 2013-2018

K van Dijk, Pieter P.A. Lestrade, Jochem B. Buil, Martha T. van der Beek, E.J. Kuijper, Greetje A. Kampinga, B.J.A. Rijnders, Alieke Vonk, Jaap Van Dissel, Sabine C. de Greeff, Annelot F. Schoffelen, Jacques F Meis, Paul E. Verweij

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We investigated the prevalence of azole resistance of AsÂpergillus fumigatus isolates in the Netherlands by screenAîng clinical A. fumigatus isolates for azole resistance during 2013-2018. We analyzed azole-resistant isolates phenoÂtypically by in vitro susceptibility testing and for the presAênce of resistance mutations in the Cyp51A gene. Over the 6-year period, 508 (11%) of 4, 496 culture-positive paÂtients harbored an azole-resistant isolate. Resistance freÂquency increased from 7.6% (95% CI 5.9%-9.8%) in 2013 (58/760 patients) to 14.7% (95% CI 12.3%-17.4%) in 2018 (112/764 patients) (p = 0.0001). TR34/L98H (69%) and TR46/Y121F/T289A (17%) accounted for 86% of Cyp51A mutaÂtions. However, the mean voriconazole MIC of TR34/L98H isolates decreased from 8 mg/L (2013) to 2 mg/L (2018), and the voriconazole-resistance frequency was 34% lower in 2018 than in 2013 (p = 0.0001). Our survey showed changing azole phenotypes in TR34/L98H isolates, which hampers the use of current PCR-based resistance tests.

Original languageEnglish
Article number32568033
Pages (from-to)1447–1455
Number of pages9
JournalEmerging Infectious Diseases
Issue number7
Publication statusPublished - Jul 2020

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