Journal
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
Volume 35, Issue 4, Pages 347-356Publisher
ELSEVIER
DOI: 10.1016/j.ijantimicag.2009.11.021
Keywords
Echinocandins; Antifungals; Synergy; Combination therapy; Candidiasis
Funding
- Biotechnology and Biological Sciences Research Council studentship [BBS/S/K/2004/11251A]
- NESTech (North East Scotland Technology Seed Fund)
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Administering synergistic combinations of antifungals could be a route to overcome problems with toxicity and the development of resistance. Combination of the echinocandins caspofungin or anidulafungin with a range of structurally diverse antimicrobial peptides resulted in potent synergistic killing of Candida spp. in vitro. Fungicidal synergy was measured by calculating fractional inhibitory concentration indices from checkerboard assays as well as loss of viability. Inhibitory combinations of the antifungals did not induce cytotoxicity in vitro. However, in a murine model of systemic candidiasis, co-administration of caspofungin with one example of the cationic peptides tested, ranalexin, did not show enhanced efficacy compared with the single treatments alone. Further study using alternative peptides will identify whether this combination approach could represent a novel treatment for fungal pathogens. (C) 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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