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

Pieter P.A. Lestrade, Jochem B. Buil, Martha T. van der Beek, E.J. Kuijper, K van Dijk, 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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