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Low level of antifungal resistance of Candida glabrata blood isolates in Turkey: Fluconazole minimum inhibitory concentration and FKS mutations can predict therapeutic failure

Mycoses · Eylül 2020

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Low level of antifungal resistance of Candida glabrata blood isolates in Turkey: Fluconazole minimum inhibitory concentration and FKS mutations can predict therapeutic failure
Mycoses · 2020 SCI-Expanded
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Makale Bilgileri

DergiMycoses
Yayın TarihiEylül 2020
Cilt / Sayfa63 · 911-920
Erişim🔓 Açık Erişim
Özet 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.

Yazarlar (13)

1
Amir Arastehfar
ORCID: 0000-0002-4361-4841
2
Farnaz Daneshnia
ORCID: 0000-0002-8782-2036
3
Mohammadreza Salehi
4
Melike Yaşar
ORCID: 0000-0001-8913-2314
5
Tuğrul Hoşbul
ORCID: 0000-0002-0150-4417
6
Macit Ilkit
ORCID: 0000-0002-1174-4182
7
Weihua Pan
ORCID: 0000-0002-3528-204X
8
Ferry Hagen
ORCID: 0000-0002-5622-1916
9
Nazlı Arslan
ORCID: 0000-0002-3951-4418
10
Hatice Türk Dağı
11
Süleyha Hilmioğlu-Polat
ORCID: 0000-0001-8850-2715
12
David S. Perlin
13
Cornelia Lass-Flörl
ORCID: 0000-0002-2946-7785

Anahtar Kelimeler

antifungal agents candidaemia Candida glabrata drug resistance genotype molecular typing

Kurumlar

Çukurova Üniversitesi Tip Fakültesi
Adana Turkey
Dokuz Eylül Üniversitesi
Izmir Turkey
Ege University Medical School
Izmir Turkey
Hackensack Meridian Health
Edison United States
Medizinische Universitat Innsbruck
Innsbruck Austria
People's Hospital
Jinan China
Selçuk Tip Fakültesi
Konya Turkey
Shanghai Key Laboratory Molecular Medical Mycology
Shanghai China
Tehran University of Medical Sciences
Tehran Iran
University Medical Center Utrecht
Utrecht Netherlands
University of Health Sciences
Istanbul Turkey
Westerdijk Fungal Biodiversity Institute - KNAW
Utrecht Netherlands

Metrikler

41
Atıf
13
Yazar
6
Anahtar Kelime

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