4.7 Article

Efficacy and pharmacodynamics of voriconazole combined with anidulafungin in azole-resistant invasive aspergillosis

Journal

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 68, Issue 2, Pages 385-393

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/jac/dks402

Keywords

azoles; echinocandins; combination therapy; synergy; additivity

Funding

  1. Gilead Sciences
  2. Merck
  3. Astellas
  4. Pfizer

Ask authors/readers for more resources

Azole resistance is an emerging problem in the treatment of Aspergillus fumigatus infections. Combination therapy may be an alternative approach to improve therapeutic outcome in azole-resistant invasive aspergillosis (IA). The in vivo efficacy of voriconazole and anidulafungin was investigated in a non-neutropenic murine model of IA using voriconazole-susceptible and voriconazole-resistant A. fumigatus clinical isolates. Treatment groups consisted of voriconazole monotherapy, anidulafungin monotherapy and voriconazoleanidulafungin at 2.5, 5, 10 and 20 mg/kg body weight/day for 7 consecutive days. In vitro and in vivo drug interactions were analysed by non-parametric Bliss independence and non-linear regression analysis. Synergistic interaction between voriconazole and anidulafungin against the voriconazole-susceptible isolate (AZN 8196) was observed in vitro and in vivo. However, among animals infected with the voriconazole-resistant isolate (V 52-35), 100 survival was observed only in groups receiving the highest doses (20 mg/kg voriconazole20 mg/kg anidulafungin). For this isolate, additivity, but not synergy, was observed in vivo. Combination of voriconazole and anidulafungin was synergistic in voriconazole-susceptible IA, but additive in voriconazole-resistant IA. There is a clear benefit of combining voriconazole and anidulafungin, but the reduced effect of combination therapy in azole-resistant IA raises some concern.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available