Skip Navigation



JAC Advance Access published online on October 27, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl392
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
58/6/1168    most recent
dkl392v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by O'Shaughnessy, E. M.
Right arrow Articles by Walsh, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by O'Shaughnessy, E. M.
Right arrow Articles by Walsh, T. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published by Oxford University Press 2006
Received April 15, 2006
Revised September 5, 2006
Accepted September 7, 2006

Original article

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

Elizabeth M. O'Shaughnessy 1, Joseph Meletiadis 1, Theodouli Stergiopoulou 1, Joanne P. Demchok 1, and Thomas J. Walsh 1 *

1 Immunocompromised Host Section, Pediatric Oncology Branch, Clinical Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

* To whom correspondence should be addressed.
Thomas J. Walsh, E-mail: walsht{at}mail.nih.gov


  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 combination of 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.

Keywords: azoles; polyenes; echinocandins; synergy; antagonism; fractional inhibitory concentration index.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
J. Meletiadis, T. Stergiopoulou, E. M. O'Shaughnessy, J. Peter, and T. J. Walsh
Concentration-Dependent Synergy and Antagonism within a Triple Antifungal Drug Combination against Aspergillus Species: Analysis by a New Response Surface Model
Antimicrob. Agents Chemother., June 1, 2007; 51(6): 2053 - 2064.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.