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JAC Advance Access originally published online on June 6, 2006
Journal of Antimicrobial Chemotherapy 2006 58(2):458-461; doi:10.1093/jac/dkl237
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© The Author 2006. 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

Caspofungin activity against clinical isolates of azole cross-resistant Candida glabrata overexpressing efflux pump genes

Brunella Posteraro1, Maurizio Sanguinetti1,*, Barbara Fiori1, Marilena La Sorda1, Teresa Spanu1, Dominique Sanglard2 and Giovanni Fadda1

1 Istituto di Microbiologia, Università Cattolica del Sacro Cuore Rome, Italy 2 Institut de Microbiologie, Centre Hospitalier Universitaire Vaudois (CHUV) Lausanne, Switzerland

Received 16 March 2006; returned 14 April 2006; revised 10 May 2006; accepted 12 May 2006

*Corresponding author. Tel: +39-06-30154964; Fax: +39-06-3051152; E-mail: msanguinetti{at}rm.unicatt.it

Objectives: Several studies have documented the potent in vitro activity of caspofungin against Candida spp. This is of special concern for Candida glabrata infections that are often resistant to many azole antifungal agents and, consequently, difficult to treat. The aim of the present study was to expand the data on the in vitro activity of caspofungin against azole-resistant isolates of C. glabrata.

Methods: A total of 50 clinical isolates of C. glabrata were tested for susceptibility to caspofungin. The isolates were cross-resistant to multiple azoles, including fluconazole, itraconazole, ketoconazole and voriconazole. Expression of the resistance-related CgCDR1 and CgCDR2 genes was evaluated by quantitative RT–PCR analysis. The MICs of caspofungin were determined by using the National Committee for Clinical Laboratory Standards M27-A2 reference method.

Results: C. glabrata isolates exhibited increased expression of the CDR efflux pump(s), and this was in accordance with their high-level azole resistance. In contrast, all the isolates were highly susceptible to caspofungin (100% of isolates were inhibited at ≤1 mg/L).

Conclusions: Our results represent further evidence for the excellent antifungal potency of caspofungin, particularly against C. glabrata isolates expressing cross-resistance to azoles.

Keywords: antifungals , susceptibility testing , CgCDR genes


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