title: Efficacy of caspofungin and voriconazole combinations in experimental aspergillosis.
abstract: Guinea pigs were infected with Aspergillus fumigatus at two challenge doses and treated for 7 days with a placebo, intraperitoneal caspofungin (1 mg/kg daily), oral voriconazole (1 mg/kg twice a day), or a combination of the caspofungin and voriconazole treatments. The combination therapy statistically significantly prolonged survival over that with the control at both challenge doses and achieved a statistically significant reduction in kidney burdens as measured by quantitative PCR. The same was true for animals given caspofungin alone at both levels of challenge and for animals treated with voriconazole alone at the lower challenge dose. However, the effects of combination therapy on prolongation of survival were greater than those of either monotherapy at both challenge doses, and the reduction in kidney burdens with combination therapy was significantly greater than that with caspofungin alone in the animals given the lower challenge dose. No synergistic interactive effects were seen for the two agents in checkerboard titration experiments in vitro. We conclude that therapy of experimental aspergillosis with caspofungin and voriconazole combined offers slight additional improvements in efficacy rather than effects of a clearly synergistic nature.
authors.affiliation: Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Donna M
authors.initials: DM
authors.lastname: MacCallum
authors.forename: Julie A
authors.initials: JA
authors.lastname: Whyte
authors.forename: Frank C
authors.initials: FC
authors.lastname: Odds
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects; D000077336:Caspofungin; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D004347:Drug Interactions; D054714:Echinocandins; D006168:Guinea Pigs; D007668:Kidney / Q000382:microbiology; D055666:Lipopeptides; D008297:Male; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D014230:Triazoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D004338:Drug Combinations; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D011743:Pyrimidines; D014230:Triazoles; D000077336:Caspofungin; D065819:Voriconazole