In Vitro Interactions between Antifungals and Immunosuppressants against Aspergillus fumigatus

William J. Steinbach, Wiley A. Schell, Jill R. Blankenship, Chiatogu Onyewu, Joseph Heitman, John R. Perfect

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1664-1669
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume48
Issue number5
DOIs
StatePublished - May 2004

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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