In Vivo Synergy of Amphotericin B plus Posaconazole in Murine Aspergillosis

Antimicrob Agents Chemother. 2015 Oct 26;60(1):296-300. doi: 10.1128/AAC.01462-15. Print 2016 Jan.

Abstract

Aspergillus fumigatus is the main mold causing invasive fungal infection that shows high mortality rates. Therapeutic failure and the increase in drug resistance make it necessary to explore alternative treatments for this infection. We have evaluated the efficacy of amphotericin B at 0.8 mg/kg or 0.3 mg/kg of body weight combined with 40 mg/kg of posaconazole against three A. fumigatus isolates in a murine model of disseminated infection. The combination of the polyene and the azole led to a greater increase in survival and a significantly greater reduction in tissue burden than monotherapies.

MeSH terms

  • Amphotericin B / pharmacology*
  • Animals
  • Antifungal Agents / pharmacology*
  • Aspergillosis / drug therapy*
  • Aspergillosis / microbiology
  • Aspergillosis / mortality
  • Aspergillosis / pathology
  • Aspergillus fumigatus / drug effects*
  • Aspergillus fumigatus / enzymology
  • Aspergillus fumigatus / genetics
  • Aspergillus fumigatus / growth & development
  • Drug Administration Schedule
  • Drug Resistance, Fungal / genetics
  • Drug Synergism
  • Gene Expression
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Kidney / drug effects
  • Kidney / microbiology
  • Lung / drug effects
  • Lung / microbiology
  • Male
  • Mice
  • Microbial Sensitivity Tests
  • Sterol 14-Demethylase / genetics*
  • Sterol 14-Demethylase / metabolism
  • Survival Analysis
  • Triazoles / pharmacology*

Substances

  • Antifungal Agents
  • Isoenzymes
  • Triazoles
  • posaconazole
  • Amphotericin B
  • Sterol 14-Demethylase