Assessing the development of oseltamivir and zanamivir resistance in A(H5N1) influenza viruses using a ferret model

Abstract

Using an in vivo ferret model, we investigated the development of resistance to oseltamivir and zanamivir for two different influenza A(H5N1) viruses (A/Vietnam/1203/2004, haemagglutinin phylogenetic clade 1, and A/Chicken/Laos/26/2006, haemagglutinin phylogenetic clade 2.3) by treating the animals with doses equivalent either to the recommended human treatment dose or a range of sub-optimal drug doses. No resistance was observed in oseltamivir-treated ferrets, but analysis of nasal washes from zanamivir-treated ferrets infected with influenza A/Vietnam/1203/2004 revealed one viral isolate (from a ferret receiving the highest dose of zanamivir, 1.0mg/kg twice daily) with a zanamivir IC50 tha..