Fluvastatin potentiates the activity of caspofungin against Aspergillus fumigatus in vitro

Suganthini Krishnan Natesan, Pranatharthi H. Chandrasekar, George J. Alangaden, Elias K. Manavathu

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Statins (anticholesterol drugs) inhibit HMG-CoA reductase, which is a key rate-limiting enzyme in the synthesis of sterols in fungi. We therefore investigated the in vitro inhibitory activity of various statins against Aspergillus fumigatus alone and in combination with antifungal drugs. Fresh conidial suspensions from 10 clinical isolates of A. fumigatus were obtained. The MIC and minimum fungicidal concentration (MFC) were determined by the Clinical and Laboratory Standards Institute M-38A protocol and the fungicidal activity by time-kill study. Fluvastatin (FST) showed good activity (MIC, 2 mg/L; MFC, 4 mg/L) against A. fumigatus; other statins had no activity (MIC ≥256 mg/L). FST enhanced the activity of caspofungin (CFG) against A. fumigatus; subinhibitory concentrations of FST in combination with CFG showed >99.9% killing of A. fumigatus conidia, whereas either drug alone showed poor activity at subinhibitory concentrations. FST potentiated the antifungal activity of CFG but displayed no specific interaction with voriconazole or amphotericin B.

Original languageEnglish (US)
Pages (from-to)369-373
Number of pages5
JournalDiagnostic Microbiology and Infectious Disease
Volume60
Issue number4
DOIs
StatePublished - Apr 1 2008

Keywords

  • Amphotericin B
  • Aspergillus fumigatus
  • Caspofungin
  • Fluvastatin
  • Fungicidal
  • Interaction
  • Kill-curve
  • Voriconazole

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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