Antifungal interactions within the triple combination of amphotericin B, caspofungin and voriconazole against Aspergillus species

Elizabeth M. O'Shaughnessy, Joseph Meletiadis, Theodouli Stergiopoulou, Joanne P. Demchok, Thomas J. Walsh

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Objectives: The in vitro effects of caspofungin combined with voriconazole and amphotericin B were tested in triplicate experiments against nine clinical isolates of Aspergillus fumigatus, Aspergillus flavus and Aspergillus terreus. Methods: The isolates were tested against a range of concentrations of voriconazole (0.015-1.0 mg/L), caspofungin (0.125-256 mg/L) and five concentrations of amphotericin B (0.1-0.5 mg/L) with a microdilution chequerboard method based on the CLSI M38-A reference method and the results were analysed with the fractional inhibitory concentration (FIC) index. The effect of individual drugs on the FIC index of each of the double combinations was also evaluated. Results: The triple combinationof voriconazole, caspofungin and amphotericin B against all Aspergillus spp. was synergistic (FIC index 0.49-0.57) at low median concentrations of amphotericin B (0.10-0.22 mg/ L) and voriconazole (0.07-0.15 mg/L) over a wide range of caspofungin concentrations (4.32-17.28 mg/L). Antagonistic interactions (FIC index 1.65-2.15) were found at higher median concentrations of amphotericin B (0.3-0.5 mg/L) and voriconazole (0.23-0.68 mg/L) over a similarly wide range of caspofungin concentrations (1.47-32 mg/L). Conclusions: These concentration-dependent interactions may have important clinical implications, which require further evaluation in animal models of invasive aspergillosis.

Original languageEnglish (US)
Pages (from-to)1168-1176
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume58
Issue number6
DOIs
StatePublished - Dec 2006
Externally publishedYes

Keywords

  • Antagonism
  • Azoles
  • Echinocandins
  • Fractional inhibitory concentration index
  • Polyenes
  • Synergy

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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