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

被引:48
|
作者
Lestrade, Pieter P. A. [1 ]
Buil, Jochem B. [2 ]
van der Beek, Martha T. [3 ]
Kuijper, Ed J. [3 ]
van Dijk, Karin [4 ]
Kampinga, Greetje A. [5 ]
Rijnders, Bart J. A. [6 ]
Vonk, Alieke G. [6 ]
de Greeff, Sabine C. [7 ]
Schoffelen, Annelot F. [7 ]
van Dissel, Jaap [7 ]
Meis, Jacques F. [2 ]
Melchers, Willem J. G. [2 ]
Verweij, Paul E. [2 ]
机构
[1] VieCuri Hosp, Venlo, Netherlands
[2] Radboud Univ Nijmegen, Canisius Wilhelmina Hosp, Ctr Expertise Mycol, Med Ctr, Nijmegen, Netherlands
[3] Leiden Univ, Med Ctr, Leiden, Netherlands
[4] Vrije Univ Amsterdam, Amsterdam Univ, Med Ctr, Amsterdam, Netherlands
[5] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands
[6] Erasmus MC, Rotterdam, Netherlands
[7] Dutch Natl Inst Publ Hlth & Environm, Ctr Infect Dis Control, Bilthoven, Netherlands
关键词
EUCAST TECHNICAL NOTE; ITRACONAZOLE; VORICONAZOLE; VALIDATION;
D O I
10.3201/eid2607.200088
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1447 / 1455
页数:9
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