Lestrade, Pieter P ABuil, Jochem Bvan der Beek, Martha TKuijper, Ed Jvan Dijk, KarinKampinga, Greetje ARijnders, Bart J AVonk, Alieke Gde Greeff, Sabine CSchoffelen, Annelot Fvan Dissel, JaapMeis, Jacques FMelchers, Willem J GVerweij, Paul E2021-05-022021-05-023256803310.3201/eid2607.200088http://hdl.handle.net/10029/624918We 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.enAspergillus fumigatusantimicrobial resistanceazole-resistantfungal infectionsfungisurveillancethe NetherlandsArticle1080-6059Emerg Infect Dis 2020; 26(7):1447-55