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Antimicrobial Agents and Chemotherapy, May 2004, p. 1664-1669, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1664-1669.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vitro Interactions between Antifungals and Immunosuppressants against Aspergillus fumigatus

Division of Pediatric Infectious Diseases, Department of Pediatrics,¹ Division of Infectious Diseases and International Health, Department of Medicine,² Department of Molecular Genetics and Microbiology,³ Department of Pharmacology and Cancer Biology,⁴ The Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710⁵

Received 8 October 2003/ Returned for modification 24 December 2003/ Accepted 19 January 2004

The optimal treatment for invasive aspergillosis remains elusive, despite the increased efficacy of newer agents. The immunosuppressants cyclosporine (CY), tacrolimus (FK506), and sirolimus (formerly called rapamycin) exhibit in vitro and in vivo activity against Candida albicans, Cryptococcus neoformans, and Saccharomyces cerevisiae, including fungicidal synergy with azole antifungals. We report here that both FK506 and CY exhibit a clear in vitro positive interaction with caspofungin against Aspergillus fumigatus by disk diffusion, microdilution checkerboard, and gross and microscopic morphological analyses. Microscopic morphological analyses indicate that the calcineurin inhibitors delay filamentation, and in combination with caspofungin there is a positive interaction. Our findings suggest a potential role for combination therapy with calcineurin pathway inhibitors and existing antifungal agents to augment activity against A. fumigatus.

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