Emerging Infectious Diseases (Jul 2020)

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,
  • Ed J. Kuijper,
  • Karin van Dijk,
  • Greetje A. Kampinga,
  • Bart J.A. Rijnders,
  • Alieke G. Vonk,
  • Sabine C. de Greeff,
  • Annelot F. Schoffelen,
  • Jaap van Dissel,
  • Jacques F. Meis,
  • Willem J.G. Melchers,
  • Paul E. Verweij

DOI
https://doi.org/10.3201/eid2607.200088
Journal volume & issue
Vol. 26, no. 7
pp. 1447 – 1455

Abstract

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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.

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