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Revision of EUCAST breakpoints: consequences for susceptibility of contemporary Danish mould isolates to isavuconazole and comparators

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@article{5eb4af23e17a4601aaf5d8d7e86f711d,
title = "Revision of EUCAST breakpoints: consequences for susceptibility of contemporary Danish mould isolates to isavuconazole and comparators",
abstract = "BACKGROUND: EUCAST recently revised the definition of the 'I' category from 'intermediate' to 'susceptible, increased exposure'. Consequently, all current antifungal breakpoints have been reviewed and revised breakpoints (v 10.0) have been released.OBJECTIVES: We investigated isavuconazole and comparator MICs (mg/L) against contemporary moulds and the consequences of the breakpoint revision for susceptibility classification.METHODS: Six hundred and ninety-six Aspergillus and 46 other moulds were included. EUCAST E.Def 10.1 azole resistance screening was performed for Aspergillus fumigatus and E.Def 9.3.1 testing of non-susceptible A. fumigatus and other moulds. Most non-wildtype/resistant isolates underwent cyp51A sequencing.RESULTS: Isavuconazole MIC50/MIC90s were ≤1/≤2 mg/L for Aspergillus flavus, A. fumigatus and Aspergillus nidulans versus 2/4 mg/L for Aspergillus niger and 2/16 mg/L for Aspergillus terreus. For the remaining moulds, MICs were highest for Fusarium (16 to >16 mg/L), lowest for dermatophytes (0.06-0.5 mg/L) and in between for Mucorales and others (1 to >16 mg/L). A very strong isavuconazole-voriconazole MIC correlation was found for A. fumigatus (Pearson r = 0.888) and itraconazole-posaconazole correlation for A. fumigatus (r = 0.905) and A. terreus (r = 0.848). For A. fumigatus, the revised breakpoints lowered isavuconazole resistance (22.6% to 7.7%, P < 0.0001) and increased voriconazole resistance (3.8% to 6.7%, P = 0.025), resulting in similar resistance rates across the four azoles (range: 6.7%-7.7%). For A. terreus, isavuconazole resistance remained unchanged (81.3%) and higher than itraconazole (43.8%, P = 0.004) and posaconazole (53.1%, P = 0.03) resistance. Azole cross-resistance was found in 24/24, 13/20 and 4/90 isolates, and Cyp51A alterations in 16/18, 1/7 and 2/4 sequenced isolates with isavuconazole MICs of >4, 4 and 2 mg/L, respectively.CONCLUSIONS: Isavuconazole displays broad anti-mould activity. The revised breakpoints result in fewer misclassifications of wildtype isolates without compromising detection of resistant mutants.",
author = "J{\o}rgensen, {Karin Meinike} and Jesus Guinea and Joseph Meletiadis and Hare, {Rasmus Kr{\o}ger} and Arendrup, {Maiken Cavling}",
note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.",
year = "2020",
month = sep,
day = "1",
doi = "10.1093/jac/dkaa212",
language = "English",
volume = "75",
pages = "2573--2581",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "9",

}

RIS

TY - JOUR

T1 - Revision of EUCAST breakpoints

T2 - consequences for susceptibility of contemporary Danish mould isolates to isavuconazole and comparators

AU - Jørgensen, Karin Meinike

AU - Guinea, Jesus

AU - Meletiadis, Joseph

AU - Hare, Rasmus Krøger

AU - Arendrup, Maiken Cavling

N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - BACKGROUND: EUCAST recently revised the definition of the 'I' category from 'intermediate' to 'susceptible, increased exposure'. Consequently, all current antifungal breakpoints have been reviewed and revised breakpoints (v 10.0) have been released.OBJECTIVES: We investigated isavuconazole and comparator MICs (mg/L) against contemporary moulds and the consequences of the breakpoint revision for susceptibility classification.METHODS: Six hundred and ninety-six Aspergillus and 46 other moulds were included. EUCAST E.Def 10.1 azole resistance screening was performed for Aspergillus fumigatus and E.Def 9.3.1 testing of non-susceptible A. fumigatus and other moulds. Most non-wildtype/resistant isolates underwent cyp51A sequencing.RESULTS: Isavuconazole MIC50/MIC90s were ≤1/≤2 mg/L for Aspergillus flavus, A. fumigatus and Aspergillus nidulans versus 2/4 mg/L for Aspergillus niger and 2/16 mg/L for Aspergillus terreus. For the remaining moulds, MICs were highest for Fusarium (16 to >16 mg/L), lowest for dermatophytes (0.06-0.5 mg/L) and in between for Mucorales and others (1 to >16 mg/L). A very strong isavuconazole-voriconazole MIC correlation was found for A. fumigatus (Pearson r = 0.888) and itraconazole-posaconazole correlation for A. fumigatus (r = 0.905) and A. terreus (r = 0.848). For A. fumigatus, the revised breakpoints lowered isavuconazole resistance (22.6% to 7.7%, P < 0.0001) and increased voriconazole resistance (3.8% to 6.7%, P = 0.025), resulting in similar resistance rates across the four azoles (range: 6.7%-7.7%). For A. terreus, isavuconazole resistance remained unchanged (81.3%) and higher than itraconazole (43.8%, P = 0.004) and posaconazole (53.1%, P = 0.03) resistance. Azole cross-resistance was found in 24/24, 13/20 and 4/90 isolates, and Cyp51A alterations in 16/18, 1/7 and 2/4 sequenced isolates with isavuconazole MICs of >4, 4 and 2 mg/L, respectively.CONCLUSIONS: Isavuconazole displays broad anti-mould activity. The revised breakpoints result in fewer misclassifications of wildtype isolates without compromising detection of resistant mutants.

AB - BACKGROUND: EUCAST recently revised the definition of the 'I' category from 'intermediate' to 'susceptible, increased exposure'. Consequently, all current antifungal breakpoints have been reviewed and revised breakpoints (v 10.0) have been released.OBJECTIVES: We investigated isavuconazole and comparator MICs (mg/L) against contemporary moulds and the consequences of the breakpoint revision for susceptibility classification.METHODS: Six hundred and ninety-six Aspergillus and 46 other moulds were included. EUCAST E.Def 10.1 azole resistance screening was performed for Aspergillus fumigatus and E.Def 9.3.1 testing of non-susceptible A. fumigatus and other moulds. Most non-wildtype/resistant isolates underwent cyp51A sequencing.RESULTS: Isavuconazole MIC50/MIC90s were ≤1/≤2 mg/L for Aspergillus flavus, A. fumigatus and Aspergillus nidulans versus 2/4 mg/L for Aspergillus niger and 2/16 mg/L for Aspergillus terreus. For the remaining moulds, MICs were highest for Fusarium (16 to >16 mg/L), lowest for dermatophytes (0.06-0.5 mg/L) and in between for Mucorales and others (1 to >16 mg/L). A very strong isavuconazole-voriconazole MIC correlation was found for A. fumigatus (Pearson r = 0.888) and itraconazole-posaconazole correlation for A. fumigatus (r = 0.905) and A. terreus (r = 0.848). For A. fumigatus, the revised breakpoints lowered isavuconazole resistance (22.6% to 7.7%, P < 0.0001) and increased voriconazole resistance (3.8% to 6.7%, P = 0.025), resulting in similar resistance rates across the four azoles (range: 6.7%-7.7%). For A. terreus, isavuconazole resistance remained unchanged (81.3%) and higher than itraconazole (43.8%, P = 0.004) and posaconazole (53.1%, P = 0.03) resistance. Azole cross-resistance was found in 24/24, 13/20 and 4/90 isolates, and Cyp51A alterations in 16/18, 1/7 and 2/4 sequenced isolates with isavuconazole MICs of >4, 4 and 2 mg/L, respectively.CONCLUSIONS: Isavuconazole displays broad anti-mould activity. The revised breakpoints result in fewer misclassifications of wildtype isolates without compromising detection of resistant mutants.

U2 - 10.1093/jac/dkaa212

DO - 10.1093/jac/dkaa212

M3 - Journal article

C2 - 32556315

VL - 75

SP - 2573

EP - 2581

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 9

ER -

ID: 62339528