Combination of caspofungin or anidulafungin with antimicrobial peptides results in potent synergistic killing of Candida albicans and Candida glabrata in vitro.
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.
Harris
Mark R
MR
Biomedical Sciences Research Complex, School of Biology, University of St Andrews, The North Haugh, St Andrews KY16 9ST, UK.
Coote
Peter J
PJ
D000077612:Anidulafungin; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight; D002176:Candida albicans / Q000187:drug effects*; D041221:Candida glabrata / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy; D000077336:Caspofungin; D015169:Colony Count, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007668:Kidney / Q000382:microbiology; D055666:Lipopeptides; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects
D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D054714:Echinocandins; D055666:Lipopeptides; D000077612:Anidulafungin; D000077336:Caspofungin