The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals against Candida parapsilosis species complex

Journal Article

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Journal of medical microbiology

J.Med.Microbiol.

Jul

Pt 7

936

944

LR: 20141120; CI: (c) 2014; JID: 0224131; 0 (Antifungal Agents); 0 (Echinocandins); 0 (Pyrimidines); 0 (Triazoles); 7XU7A7DROE (Amphotericin B); 83HN0GTJ6D (Cyclosporine); F0XDI6ZL63 (caspofungin); JFU09I87TR (Voriconazole); 2014/04/10 [aheadofprint]; ppu

England

1473-5644; 0022-2615

PMID: 24722799

eng

Journal Article; Research Support, Non-U.S. Gov't; IM

10.1099/jmm.0.073478-0 [doi]

Unknown(0)

24722799

Candida parapsilosis complex comprises three closely related species, C. parapsilosis sensu stricto, Candida metapsilosis and Candida orthopsilosis. In the last decade, antifungal resistance to azoles and caspofungin among C. parapsilosis sensu lato strains has been considered a matter of concern worldwide. In the present study, we evaluated the synergistic potential of antifungals and the calcineurin inhibitor cyclosporin A (Cys) against planktonic and biofilms of C. parapsilosis complex from clinical sources. Susceptibility assays with amphotericin, fluconazole, voriconazole, caspofungin and Cys were performed by microdilution in accordance with Clinical and Laboratory Standards Institute guidelines. Synergy testing against planktonic cells of C. parapsilosis sensu lato strains was assessed by the chequerboard method. Combinations formed by antifungals with Cys were evaluated against mature biofilms in microtitre plates. No differences in the antifungal susceptibility pattern among species were observed, but C. parapsilosis sensu stricto strains were more susceptible to Cys than C. orthopsilosis and C. metapsilosis. Synergism between antifungals and Cys was observed in C. parapsilosis sensu lato strains. Combinations formed by antifungals and Cys were able to prevent biofilm formation and showed an inhibitory effect against mature biofilms of C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis. These results strengthen the potential of calcineurin inhibition as a promising approach to enhance the efficiency of antifungal drugs.

The Authors

Cordeiro Rde,A., Macedo Rde,B., Teixeira,C.E., Marques,F.J., Bandeira Tde,J., Moreira,J.L., Brilhante,R.S., Rocha,M.F., Sidrim,J.J.

Department of Pathology and Legal Medicine, School of Medicine, Postgraduate Program in Medical Microbiology and Specialized Medical Mycology Center, Federal University of Ceara, Fortaleza, Ceara, Brazil Department of Clinical Medicine, School of Medicine

20140410

http://vp9py7xf3h.search.serialssolutions.com/?charset=utf-8&pmid=24722799

2014