Exposure-response relationships of voriconazole in combination with anidulafungin in a non-neutropenic murine model of resistant Aspergillus fumigatus infection

Ref ID: 17728


S. Seyedmousavi*, R.J.M. Bruggemann, W.J.G. Melchers, J.W. Mouton,
P.E. Verweij

Author address:

(Nijmegen, NL)

Full conference title:

22nd European Congress of Clinical Microbiology and Infectious Diseases


Objectives: In an era of increasing emergence of azole-resistance in
Aspergillus fumigatus, combining antifungal agents may be an
alternative approach to improve therapeutic outcomes in azoleresistant
invasive aspergillosis (IA). The efficacies of antifungal
agents can be described by pharmacodynamic indices (PDIs), such as
area under the concentration-time curve above the MIC (AUC > MIC).
We explored whether the same PDIs that explain efficacy during
monotherapy would explain efficacy during combination therapy in an
animal model of IA.
Methods: Female CD-1 mice were infected intravenously 24 hours
prior to start therapy with VCZ-susceptible and VCZ-resistant
Aspergillus fumigatus. Fourteen days efficacy data (survival) were
determined for various combination regimens of 2.5, 5, 10 and 20 mg/
kg voriconazole (VCZ) plus anidulafungin (AFG) and for each of these
agents singly. Groups of 11 mice were treated intraperitoneally once
daily, for seven consecutive days. The parameters for each dose as
determined from pharmacokinetic experiments, was used to calculate
PDI for each strain. Multiple regression analysis was used to determine
the importance of various PDIs during monotherapy. The efficacies of
the combination regimens were then predicted on the basis of a linear
regression analysis for the single agents with the highest r2 value and

Abstract Number: NULL

Conference Year: 2012

Link to conference website: NULL

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