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:10.3201/eid2607.200088

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^*

^*Corresponding author for this work

VieCuri Medisch Centrum
Radboud University Medical Center
Leiden University
Amsterdam UMC - Vrije Universiteit Amsterdam
University of Groningen, University Medical Center Groningen
Erasmus University Rotterdam
National Institute of Public Health and the Environment

Research output: Contribution to journal › Review article › Academic › peer-review

Abstract

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 language	English
Pages (from-to)	1447-1455
Number of pages	9
Journal	Emerging infectious diseases
Volume	26
Issue number	7
DOIs	https://doi.org/10.3201/eid2607.200088
Publication status	Published - 1 Jul 2020
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.3201/eid2607.200088

Cite this

Lestrade, P. P. A., Buil, J. B., van der Beek, M. T., Kuijper, E. J., Dijk, K. V., Kampinga, G. A., Rijnders, B. J. A., Vonk, A. G., de Greeff, S. C., Schoffelen, A. F., Dissel, J. V., Meis, J. F., Melchers, W. J. G., & Verweij, P. E. (2020). Paradoxal Trends in Azole-Resistant Aspergillus fumigatus in a National Multicenter Surveillance Program, the Netherlands, 2013-2018. Emerging infectious diseases, 26(7), 1447-1455. https://doi.org/10.3201/eid2607.200088

@article{43a7c1761fdc4c63a51b539a7b0b3fad,

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

abstract = "We investigated the prevalence of azole resistance of As{\^A}pergillus fumigatus isolates in the Netherlands by screenA{\^i}ng clinical A. fumigatus isolates for azole resistance during 2013-2018. We analyzed azole-resistant isolates pheno{\^A}typically by in vitro susceptibility testing and for the presA{\^e}nce of resistance mutations in the Cyp51A gene. Over the 6-year period, 508 (11\%) of 4, 496 culture-positive pa{\^A}tients harbored an azole-resistant isolate. Resistance fre{\^A}quency 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 muta{\^A}tions. 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.",

author = "Lestrade, \{Pieter P. A.\} and Buil, \{Jochem B.\} and \{van der Beek\}, \{Martha T.\} and Kuijper, \{Ed J.\} and Dijk, \{Karin Van\} and Kampinga, \{Greetje A.\} and Rijnders, \{Bart J. A.\} and Vonk, \{Alieke G.\} and \{de Greeff\}, \{Sabine C.\} and Schoffelen, \{Annelot F.\} and Dissel, \{Jaap Van\} and Meis, \{Jacques F.\} and Melchers, \{Willem J. G.\} and Verweij, \{Paul E.\}",

year = "2020",

month = jul,

day = "1",

doi = "10.3201/eid2607.200088",

language = "English",

volume = "26",

pages = "1447--1455",

journal = "Emerging infectious diseases",

issn = "1080-6040",

publisher = "Centers for Disease Control and Prevention (CDC)",

number = "7",

}

Lestrade, PPA, Buil, JB, van der Beek, MT, Kuijper, EJ, Dijk, KV, Kampinga, GA, Rijnders, BJA, Vonk, AG, de Greeff, SC, Schoffelen, AF, Dissel, JV, Meis, JF, Melchers, WJG & Verweij, PE 2020, 'Paradoxal Trends in Azole-Resistant Aspergillus fumigatus in a National Multicenter Surveillance Program, the Netherlands, 2013-2018', Emerging infectious diseases, vol. 26, no. 7, pp. 1447-1455. https://doi.org/10.3201/eid2607.200088

Paradoxal Trends in Azole-Resistant Aspergillus fumigatus in a National Multicenter Surveillance Program, the Netherlands, 2013-2018. / Lestrade, Pieter P. A.; Buil, Jochem B.; van der Beek, Martha T. et al.
In: Emerging infectious diseases, Vol. 26, No. 7, 01.07.2020, p. 1447-1455.

Research output: Contribution to journal › Review article › Academic › peer-review

TY - JOUR

T1 - Paradoxal Trends in Azole-Resistant Aspergillus fumigatus in a National Multicenter Surveillance Program, the Netherlands, 2013-2018

AU - Lestrade, Pieter P. A.

AU - Buil, Jochem B.

AU - van der Beek, Martha T.

AU - Kuijper, Ed J.

AU - Dijk, Karin Van

AU - Kampinga, Greetje A.

AU - Rijnders, Bart J. A.

AU - Vonk, Alieke G.

AU - de Greeff, Sabine C.

AU - Schoffelen, Annelot F.

AU - Dissel, Jaap Van

AU - Meis, Jacques F.

AU - Melchers, Willem J. G.

AU - Verweij, Paul E.

PY - 2020/7/1

Y1 - 2020/7/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85086832653

U2 - 10.3201/eid2607.200088

DO - 10.3201/eid2607.200088

M3 - Review article

C2 - 32568033

SN - 1080-6040

VL - 26

SP - 1447

EP - 1455

JO - Emerging infectious diseases

JF - Emerging infectious diseases

IS - 7

ER -

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

Abstract

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