Low level of antifungal resistance ofCandida glabratablood isolates in Turkey: Fluconazole minimum inhibitory concentration andFKSmutations can predict therapeutic failure

Arastehfar A., Daneshnia F., Salehi M., Yasar M., Hosbul T., Ilkit M., ...Daha Fazla

MYCOSES, cilt.63, sa.9, ss.911-920, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 63 Sayı: 9
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1111/myc.13104
  • Dergi Adı: MYCOSES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.911-920
  • Anahtar Kelimeler: antifungal agents, Candida glabrata, candidaemia, drug resistance, genotype, molecular typing, INVASIVE CANDIDIASIS, ECHINOCANDIN RESISTANCE, CASPOFUNGIN RESISTANCE, CHANGING EPIDEMIOLOGY, BROTH MICRODILUTION, EUCAST METHODS, SUSCEPTIBILITY, SURVEILLANCE, SECONDARY, TROPICALIS
  • Çukurova Üniversitesi Adresli: Evet

Özet

Background Candida glabratais 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 ofCglabratablood 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 ofPDR1andFKS1/2hotspots (HSs). Results Candida glabrataprevalence in Ege University Hospital was twofold higher in 2014-2019 than in 2005-2014. Six of the analysed isolates had fluconazole MICs >= 32 mu g/mL; of them, five harboured uniquePDR1mutations. 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-FKSmutations and/or demonstrating fluconazole MIC >= 32 mu g/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-FKSsequencing to predict TF for echinocandins, whereas fluconazole MIC >= 32 mu g/mL may predict TF. Recent emergence ofC glabrataisolates associated with antifungal TF warrants future comprehensive prospective studies in Turkey.