Low level of antifungal resistance of Candida glabrata blood isolates in Turkey : Fluconazole minimum inhibitory concentration and FKS mutations can predict therapeutic failure
© 2020 The Authors. Mycoses published by Blackwell Verlag GmbH..
BACKGROUND: Candida glabrata is the third leading cause of candidaemia in Turkey; however, the data regarding antifungal resistance mechanisms and genotypic diversity in association with their clinical implication are limited.
OBJECTIVES: To assess genotypic diversity, antifungal susceptibility and mechanisms of drug resistance of C glabrata blood isolates and their association with patients' outcome in a retrospective multicentre study.
PATIENTS/METHODS: Isolates from 107 patients were identified by ITS sequencing and analysed by multilocus microsatellite typing, antifungal susceptibility testing, and sequencing of PDR1 and FKS1/2 hotspots (HSs).
RESULTS: Candida glabrata prevalence in Ege University Hospital was twofold higher in 2014-2019 than in 2005-2014. Six of the analysed isolates had fluconazole MICs ≥ 32 µg/mL; of them, five harboured unique PDR1 mutations. Although echinocandin resistance was not detected, three isolates had mutations in HS1-Fks1 (S629T, n = 1) and HS1-Fks2 (S663P, n = 2); one of the latter was also fluconazole-resistant. All patients infected with isolates carrying HS-FKS mutations and/or demonstrating fluconazole MIC ≥ 32 µg/mL (except one without clinical data) showed therapeutic failure (TF) with echinocandin and fluconazole; seven such isolates were collected in Ege (n = 4) and Gulhane (n = 3) hospitals and six detected recently. Among 34 identified genotypes, none were associated with mortality or enriched for fluconazole-resistant isolates.
CONCLUSION: Antifungal susceptibility testing should be supplemented with HS-FKS sequencing to predict TF for echinocandins, whereas fluconazole MIC ≥ 32 µg/mL may predict TF. Recent emergence of C glabrata isolates associated with antifungal TF warrants future comprehensive prospective studies in Turkey.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:63 |
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| Enthalten in: |
Mycoses - 63(2020), 9 vom: 01. Sept., Seite 911-920 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Arastehfar, Amir [VerfasserIn] |
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| Links: |
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| Themen: |
8VZV102JFY |
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| Anmerkungen: |
Date Completed 12.07.2021 Date Revised 12.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/myc.13104 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM309958571 |
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| 245 | 1 | 0 | |a Low level of antifungal resistance of Candida glabrata blood isolates in Turkey |b Fluconazole minimum inhibitory concentration and FKS mutations can predict therapeutic failure |
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| 500 | |a Date Revised 12.07.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Authors. Mycoses published by Blackwell Verlag GmbH. | ||
| 520 | |a BACKGROUND: Candida glabrata is the third leading cause of candidaemia in Turkey; however, the data regarding antifungal resistance mechanisms and genotypic diversity in association with their clinical implication are limited | ||
| 520 | |a OBJECTIVES: To assess genotypic diversity, antifungal susceptibility and mechanisms of drug resistance of C glabrata blood isolates and their association with patients' outcome in a retrospective multicentre study | ||
| 520 | |a PATIENTS/METHODS: Isolates from 107 patients were identified by ITS sequencing and analysed by multilocus microsatellite typing, antifungal susceptibility testing, and sequencing of PDR1 and FKS1/2 hotspots (HSs) | ||
| 520 | |a RESULTS: Candida glabrata prevalence in Ege University Hospital was twofold higher in 2014-2019 than in 2005-2014. Six of the analysed isolates had fluconazole MICs ≥ 32 µg/mL; of them, five harboured unique PDR1 mutations. Although echinocandin resistance was not detected, three isolates had mutations in HS1-Fks1 (S629T, n = 1) and HS1-Fks2 (S663P, n = 2); one of the latter was also fluconazole-resistant. All patients infected with isolates carrying HS-FKS mutations and/or demonstrating fluconazole MIC ≥ 32 µg/mL (except one without clinical data) showed therapeutic failure (TF) with echinocandin and fluconazole; seven such isolates were collected in Ege (n = 4) and Gulhane (n = 3) hospitals and six detected recently. Among 34 identified genotypes, none were associated with mortality or enriched for fluconazole-resistant isolates | ||
| 520 | |a CONCLUSION: Antifungal susceptibility testing should be supplemented with HS-FKS sequencing to predict TF for echinocandins, whereas fluconazole MIC ≥ 32 µg/mL may predict TF. Recent emergence of C glabrata isolates associated with antifungal TF warrants future comprehensive prospective studies in Turkey | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Hoşbul, Tuğrul |e verfasserin |4 aut | |
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| 700 | 1 | |a Perlin, David S |e verfasserin |4 aut | |
| 700 | 1 | |a Lass-Flörl, Cornelia |e verfasserin |4 aut | |
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