alexa Molecular Characterization and In Vitro Antifungal Susceptibility of Candida Glabrata Clinical Isolates with Reduced Echinocandin Susceptibility and High Level Multi-Azole Resistance
ISSN: 2327-5073

Clinical Microbiology: Open Access
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Case Report

Molecular Characterization and In Vitro Antifungal Susceptibility of Candida Glabrata Clinical Isolates with Reduced Echinocandin Susceptibility and High Level Multi-Azole Resistance

Jose A Vazquez1,3,4*, Dwayne Baxa1, Merideth Wierman1, Karam Obeid2, Dora Vager1 and Elias Manavathu1,4

1Division of Infectious Diseases, Henry Ford Hospital, USA

2Division of Infectious Diseases, St. John Health System, USA

3Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, Michigan, USA

4Division of Infectious Diseases, Medical College of Georgia at Georgia Regent’s University, Augusta, GA, USA

*Corresponding Author:
Jose A. Vazquez
Georgia Regents University, Augusta, GA, USA
Tel: 706-723-0105
Fax: 707-721-4517
E-mail: [email protected]

Received Date: March 29, 2014; Accepted Date: May 07, 2014; Published Date: June 13, 2014

Citation: Vazquez JA, Baxa D, Wierman M, Obeid K, Vager D, et al. (2014) Molecular Characterization and In Vitro Antifungal Susceptibility of Candida Glabrata Clinical Isolates with Reduced Echinocandin Susceptibility and High Level Multi-Azole Resistance. Clin Microbial 3:154. doi: 10.4172/2327-5073.1000154

Copyright: © 2014 Vazquez JA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Candida glabrata is the second most commonly isolated yeast recovered from blood cultures in the United States. We characterized 85 C. glabrata clinical isolates recovered from various clinical specimens obtained from immunocompromised individuals. This collection was unique because it included a series of isolates recovered from the blood of a patient who only partially responded to antifungal therapy. In vitro activity of caspofungin, micafungin, anidulafungin, fluconazole, voriconazole and amphotericin B was evaluated. Most of the isolates were susceptible to the echinocandins, triazoles and amphotericin B. The geometric mean MIC of the antifungals for the susceptible isolates (n=79) were as follows: caspofungin, 0.061315 ± 0.076934; micafungin, 0.123521 ± 0.457202; anidulafungin, 0.044158 ± 0.895249; fluconazole, 7.013461 ± 20.56794; voriconazole, 0.324939 ± 1.051247; amphotericin B, 0.474923 ± 0.162994. Five of the six serial blood isolates showed a reduced echinocandin susceptibility (RES) to the echinocandins and the triazoles. Characterization of the hot spot 1 region of FKS1, FKS2 and FKS3 showed no amino acid alterations. However, the genes coding for the drug efflux proteins CgCDR1, CgCDR2, CgSNQ2, as well as Cgcyp51 were over-expressed in the isolates with RES and azole resistance compared to the susceptible isolates, indicating that the upregulation of the synthesis of efflux proteins and the drug target is responsible for conferring resistance to triazoles in these isolates. These results demonstrate that multiechinocandin and multi-azole resistant C. glabrata clinical isolates can emerge under the selection pressure imposed by specific drug therapy over a relatively short period of time.

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