Combination therapy in treatment of experimental pulmonary aspergillosis: synergistic interaction between an antifungal triazole and an echinocandin

J Infect Dis. 2003 Jun 15;187(12):1834-43. doi: 10.1086/375420. Epub 2003 Jun 4.


Invasive pulmonary aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Simultaneous inhibition of fungal cell-wall and cell-membrane biosynthesis may result in synergistic interaction against Aspergillus fumigatus. We studied the antifungal activity of micafungin, a new echinocandin, in combination with ravuconazole, a second-generation triazole, against experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. This combination led to significant reductions in mortality (P</=.001), residual fungal burden (P</=.05), and serum galactomannan antigenemia (P</=.01), compared with either agent alone. Combination therapy also resulted in reduction (P</=.05) of organism-mediated pulmonary injury and of pulmonary infiltrates detected by thoracic computed tomography (P</=.001). No toxicity was observed with the echinocandin-triazole combination. An MTT hyphal damage assay demonstrated significant in vitro synergistic interaction between the antifungal triazole and the echinocandin. The combination of an antifungal triazole and echinocandin may represent a new strategy for treatment of invasive pulmonary aspergillosis.

MeSH terms

  • Animals
  • Aspergillosis / drug therapy*
  • Aspergillus fumigatus / drug effects
  • Disease Models, Animal
  • Drug Synergism
  • Drug Therapy, Combination
  • Echinocandins
  • Female
  • Lipopeptides
  • Lipoproteins / administration & dosage*
  • Lipoproteins / blood
  • Lipoproteins / therapeutic use*
  • Lung / pathology
  • Lung Diseases, Fungal / drug therapy*
  • Micafungin
  • Organ Size
  • Peptides, Cyclic / administration & dosage*
  • Peptides, Cyclic / blood
  • Peptides, Cyclic / therapeutic use*
  • Rabbits
  • Thiazoles / administration & dosage*
  • Thiazoles / blood
  • Thiazoles / therapeutic use*
  • Triazoles / administration & dosage*
  • Triazoles / blood
  • Triazoles / therapeutic use*


  • Echinocandins
  • Lipopeptides
  • Lipoproteins
  • Peptides, Cyclic
  • Thiazoles
  • Triazoles
  • ER 30346
  • Micafungin