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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We investigated the prevalence of azole resistance of Aspergillus fumigatus isolates in the Netherlands by screening clinical A. fumigatus isolates for azole resistance during 2013-2018. We analyzed azole-resistant isolates phenotypically by in vitro susceptibility testing and for the presence of resistance mutations in the Cyp51A gene. Over the 6-year period, 508 (11%) of 4,496 culture-positive patients harbored an azole-resistant isolate. Resistance frequency 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 mutations. 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
Volume26
Issue number7
DOIs
Publication statusPublished - Jul 2020

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