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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 Publisher Pubmed



Arastehfar A1, 2 ; Daneshnia F1 ; Salehi M3 ; Yasar M4 ; Hosbul T5 ; Ilkit M6 ; Pan W1 ; Hagen F2, 7, 8 ; Arslan N9 ; Turkdagi H10 ; Hilmioglupolat S4 ; Perlin DS11 ; Lassflorl C12
Authors
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Authors Affiliations
  1. 1. Shanghai Key Laboratory Molecular Medical Mycology, Shanghai, China
  2. 2. Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands
  3. 3. Department of Infectious Diseases and Tropical Medicine, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Medical Microbiology, Faculty of Medicine, Ege University, Izmir, Turkey
  5. 5. Department of Medical Microbiology, Gulhane Training and Research Hospital, University of Health Sciences, Ankara, Turkey
  6. 6. Division of Mycology, Faculty of Medicine, Cukurova University, Adana, Turkey
  7. 7. University Medical Center Utrecht, Utrecht, Netherlands
  8. 8. People's Hospital, Jining, China
  9. 9. Department of Medical Microbiology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey
  10. 10. Department of Microbiology, Faculty of Medicine, Selcuk University, Konya, Turkey
  11. 11. Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United States
  12. 12. Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria

Source: Mycoses Published:2020


Abstract

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. © 2020 The Authors. Mycoses published by Blackwell Verlag GmbH
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