Efficacy of caspofungin and voriconazole combinations in experimental aspergillosis

D M MacCallum, Julie A. Whyte, F C Odds

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Guinea pigs were infected with Aspergillus fumigatus at two, challenge doses and treated for 7 days with a placebo, intraperitoneal caspofungin (I mg/kg daily), oral voriconazole (I 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.

Original languageEnglish
Pages (from-to)3697-3701
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume49
DOIs
Publication statusPublished - 2005

Keywords

  • ECHINOCANDIN CASPOFUNGIN
  • INVASIVE ASPERGILLOSIS
  • ANTIFUNGAL AGENT
  • MURINE MODEL
  • GUINEA-PIG
  • FUMIGATUS
  • DISPOSITION
  • ACETATE
  • THERAPY
  • MK-0991

Cite this

Efficacy of caspofungin and voriconazole combinations in experimental aspergillosis. / MacCallum, D M ; Whyte, Julie A.; Odds, F C .

In: Antimicrobial Agents and Chemotherapy, Vol. 49, 2005, p. 3697-3701.

Research output: Contribution to journalArticle

@article{1422a10e327d484482cb6e8fb1db5ccd,
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 (I mg/kg daily), oral voriconazole (I 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.",
keywords = "ECHINOCANDIN CASPOFUNGIN, INVASIVE ASPERGILLOSIS, ANTIFUNGAL AGENT, MURINE MODEL, GUINEA-PIG, FUMIGATUS, DISPOSITION, ACETATE, THERAPY, MK-0991",
author = "MacCallum, {D M} and Whyte, {Julie A.} and Odds, {F C}",
year = "2005",
doi = "10.1128/AAC.49.9.3697-3701.2005",
language = "English",
volume = "49",
pages = "3697--3701",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "AMER SOC MICROBIOLOGY",

}

TY - JOUR

T1 - Efficacy of caspofungin and voriconazole combinations in experimental aspergillosis

AU - MacCallum, D M

AU - Whyte, Julie A.

AU - Odds, F C

PY - 2005

Y1 - 2005

N2 - Guinea pigs were infected with Aspergillus fumigatus at two, challenge doses and treated for 7 days with a placebo, intraperitoneal caspofungin (I mg/kg daily), oral voriconazole (I 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.

AB - Guinea pigs were infected with Aspergillus fumigatus at two, challenge doses and treated for 7 days with a placebo, intraperitoneal caspofungin (I mg/kg daily), oral voriconazole (I 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.

KW - ECHINOCANDIN CASPOFUNGIN

KW - INVASIVE ASPERGILLOSIS

KW - ANTIFUNGAL AGENT

KW - MURINE MODEL

KW - GUINEA-PIG

KW - FUMIGATUS

KW - DISPOSITION

KW - ACETATE

KW - THERAPY

KW - MK-0991

U2 - 10.1128/AAC.49.9.3697-3701.2005

DO - 10.1128/AAC.49.9.3697-3701.2005

M3 - Article

VL - 49

SP - 3697

EP - 3701

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

ER -