Low level of antifungal resistance in iranian isolates of candida glabrata recovered from blood samples in a multicenter study from 2015 to 2018 and potential prognostic values of genotyping and sequencing of PDR1

Arastehfar, A. and Daneshnia, F. and Zomorodian, K. and Najafzadeh, M. J. and Khodavaisy, S. and Zarrinfar, H. and Hagen, F. and Shahrabadi, Z. Z. and Lackner, M. and Mirhendi, H. and Salehi, M. and Roudbary, M. and Pan, W. and Kostrzewa, M. and Boekhout, T. (2019) Low level of antifungal resistance in iranian isolates of candida glabrata recovered from blood samples in a multicenter study from 2015 to 2018 and potential prognostic values of genotyping and sequencing of PDR1. Antimicrobial Agents and Chemotherapy, 63 (7).

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Low level of antifungal resistance in iranian isolates of candida glabrata recovered from blood samples in a multicenter study from 2015 to 2018 and potential prognostic values of genotyping and sequencing of PDR1.pdf

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Abstract

Establishing an effective empirical antifungal therapy requires that national surveillance studies be conducted. Herein, we report the clinical outcome of infections with and the microbiological features of Iranian isolates of Candida glabrata derived from patients suffering from candidemia. C. glabrata isolates were retrospectively collected from four major cities in Iran; identified by a 21-plex PCR, matrix-assisted laser desorption ionization–time of flight mass spectrometry, and large subunit of ribosomal DNA sequencing; and genotyped by amplified fragment length polymorphism (AFLP). Mutations in PDR1, ERG11, and hot spot 1 (HS1) of FKS1 and FKS2 were investigated, and antifungal susceptibility testing (AFST) was performed (by the CLSI M27-A3 and M27-S4 methods). Seventy isolates of C. glabrata were collected from 65 patients with a median age of 58 years. Fluconazole was the most widely used (29.23) and least effective antifungal agent. The overall crude mortality rate was 35.4. Only one strain was resistant to fluconazole, and 57.7 and 37.5 of the isolates were non-wild type (non-WT) for susceptibility to caspofungin and voriconazole, respectively. All isolates showed the WT phenotype for amphotericin B, posaconazole, and itraconazole. HS1 of FKS1 and FKS2 did not harbor any mutations, while numerous missense mutations were observed in PDR1 and ERG11. AFLP clustered our isolates into nine genotypes; among them, genotypes 1 and 2 were significantly associated with a higher mortality rate (P 0.034 and P 0.022, 0.05). Moreover, 83.3 of patients infected with strains harboring a single new mutation in PDR1, T745A, died despite treatment with fluconazole or caspofungin. Overall, Iranian isolates of C. glabrata were susceptible to the major antifungal drugs. Application of genotyping techniques and sequencing of a specific gene (PDR1) might have prognostic implications. Copyright © 2019 Arastehfar et al.

Item Type: Article
Additional Information: Cited By :2 Export Date: 16 February 2020 CODEN: AMACC Correspondence Address: Roudbary, M.; Department of Medical Mycology and Parasitology, School of Medicine, Iran University of Medical SciencesIran; email: Roudbari.mr@iums.ac.ir
Uncontrolled Keywords: Antifungal susceptibility testing Candida glabrata Candidemia CgPDR1 ERG11 Genotyping HS1 of FKS1 and FKS2 Iran amphotericin B antifungal agent caspofungin fluconazole itraconazole posaconazole ribosome DNA voriconazole adult amplified fragment length polymorphism antifungal resistance antifungal susceptibility Article blood sampling clinical outcome female fungus isolation genotype genotyping technique human major clinical study male matrix assisted laser desorption ionization time of flight mass spectrometry missense mutation mortality rate phenotype priority journal retrospective study
Subjects: QW Microbiology and Immunology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib1 lib1
Date Deposited: 20 Jun 2020 09:10
Last Modified: 20 Jun 2020 09:10
URI: http://eprints.mums.ac.ir/id/eprint/18258

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