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

Seyedmojtaba Seyedmousavi, Roger J.M. Brüggemann, Willem J.G. Melchers, Antonius J.M.M. Rijs, Paul E. Verweij, Johan W. Mouton

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

60 Citaten (Scopus)


Objectives: 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. Methods: Treatment groups consisted of voriconazole monotherapy, anidulafungin monotherapy and voriconazole + anidulafungin 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. Results: 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 voriconazole + 20 mg/kg anidulafungin). For this isolate, additivity, but not synergy, was observed in vivo. Conclusions: 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.

Originele taal-2Engels
Pagina's (van-tot)385-393
Aantal pagina's9
TijdschriftJournal of Antimicrobial Chemotherapy
Nummer van het tijdschrift2
StatusGepubliceerd - feb. 2013
Extern gepubliceerdJa


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