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JAC Advance Access originally published online on April 27, 2007
Journal of Antimicrobial Chemotherapy 2007 59(6):1076-1083; doi:10.1093/jac/dkm095
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Acquired resistance to echinocandins in Candida albicans: case report and review

Marie-Thérèse Baixench1, Naji Aoun2, Marie Desnos-Ollivier3, Dea Garcia-Hermoso3, Stéphane Bretagne3, Sandrine Ramires2, Christophe Piketty2 and Eric Dannaoui1,3,*

1 Université Paris Descartes, Faculté de Médecine, AP-HP, Hôpital Européen Georges Pompidou, Unité de Parasitologie—Mycologie, 75015 Paris, France 2 Service d'Immunologie Clinique, Hôpital Européen Georges Pompidou, AP-HP, Paris, France 3 Centre National de Référence Mycologie et Antifongiques, Unité de Mycologie Moléculaire, CNRS URA 3012, Institut Pasteur, 75724 Paris Cedex 15, France

Received 4 January 2007; returned 18 February 2007; revised 7 March 2007; accepted 7 March 2007

* Correspondence address. Centre National de Référence Mycologie et Antifongiques, Unité de Mycologie Moléculaire, CNRS URA3012, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Tel: +33-1-40-61-32-50; Fax: +33-1-45-68-84-20; E-mail: dannaoui{at}pasteur.fr

Objectives: A patient with Candida albicans thrush and oesophagitis was treated with high doses of caspofungin but treatment eventually failed. Four C. albicans isolates were serially recovered before and after caspofungin treatment. A microbiological study was performed to characterize these four isolates.

Methods: In vitro antifungal susceptibility testing was performed by the EUCAST reference method in RPMI and AM3 and by Etest®. Molecular typing of the four isolates was done by sizing three polymorphic microsatellite markers. To look for specific mutations, sequencing of a region of the gene encoding the 1-3-ß-D-glucan synthase was performed for the four isolates.

Results: In vitro antifungal susceptibility testing showed an increase in both caspofungin and micafungin MICs for the two isolates recovered after caspofungin treatment failure. The best discrimination between the pre-treatment and post-treatment isolates was obtained with Etest®. Molecular typing of the four isolates showed that the post-treatment isolates with reduced susceptibility were identical to a susceptible pre-treatment isolate, suggesting the acquisition of caspofungin resistance. Sequencing of the gene encoding the 1-3-ß-D-glucan synthase showed a mutation responsible for an amino acid change at Phe-641 that could confer reduced susceptibility to both echinocandins.

Conclusions: Our results indicate that is it useful to perform in vitro susceptibility testing in the cases of clinical failure during caspofungin therapy.

Keywords: caspofungin , micafungin , 1-3-ß-D-glucan synthase , Etest


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