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JAC Advance Access first published online on January 13, 2008
This version published online on January 22, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm493
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© The Author 2008. 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

In vitro interaction between azoles and cyclosporin A against clinical isolates of Candida albicans determined by the chequerboard method and time–kill curves

Yan Li1, Shujuan Sun1,*, Qiongjie Guo2, Lin Ma2, Changwen Shi3, Lequn Su1 and Hongjian Li1

1 Department of Pharmacy, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, People's Republic of China 2 School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong Province, People's Republic of China 3 The General Surgical Central Laboratory of Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, People's Republic of China

Received 20 July 2007; returned 3 October 2007; revised 19 October 2007; accepted 23 November 2007

* Corresponding author. Tel: +86-531-89268366; Fax: +86-531-82961267; E-mail: sunshujuan888{at}163.com

Objectives: To investigate the in vitro interaction between three azoles (fluconazole, itraconazole and voriconazole) and cyclosporin A against five azole-susceptible (azole-S) and five azole-resistant (azole-R) clinical Candida albicans isolates.

Methods: By using a chequerboard technique and time–kill curves, synergistic, indifferent or antagonistic effects when drugs were used in combination were assessed. In the chequerboard assay, the antifungal activity of drug combinations was determined by the microdilution method based on the CLSI M27-A2 guidelines. The effects of the interactions were assessed by two non-parametric approaches (fractional inhibitory concentration index model and {Delta}E model). In the time–kill assay, a colony counting method was employed against one azole-S strain and one azole-R strain at 0, 6, 12, 24 and 48 h of incubation at 35°C.

Results: Good concordance was found between the chequerboard method and time–kill curves. Indifference or synergism was observed for azole-S isolates in interactions of azoles and cyclosporin A, while strong synergism was observed for azole-R isolates in all drug combinations.

Conclusions: Cyclosporin A showed potent synergism when combined with the three azoles, especially against azole-R C. albicans strains, and there was good agreement between various methods used in this study.

Key Words: microdilution , spectrophotometric method , non-parametric approaches , colony counting


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