Amantadine-resistant influenza a virus in Taiwan

Background and purpose: Amantadine and rimantadine have been used for treatment and prophylaxis of influenza A virus infection. We examined the amantadine susceptibility of field isolates of influenza A virus in Taiwan from 1996 to 1998 to monitor the presence of resistant strains. Methods: Eighty-four field isolates of influenza A virus were examined for resistance to amantadine by plaque inhibition assay. Virus isolates with amantadine 50% inhibitory concentrations (IC₅₀) greater than 0.9 μg were chosen for sequence analysis of the M gene that is the molecular target for amantadine/rimantadine. Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify the viral RNA. RT-PCR products were examined and purified by agarose gel electrophoresis for further sequence analysis. The Genetics Computer Group Sequence Analysis Package and the neighbor-joining method listed in the Molecular Evolutionary Genetic Analysis package were used for phylogenetic analysis. Results: One field strain was amantadine resistant (IC₅₀ > 10 μg/mL), with a mutation (position 31, serine to asparagine) in the M2 protein. The resistant virus was isolated from a non-immunocompromised child without a history of amantadine/rimantadine treatment. None of the family members reported previous exposure to amantadine/rimantadine. Conclusions: In this series, amantadine-resistant influenza A (H1N1) virus was isolated from a non-immunocompromised Taiwanese child without a known history of exposure to this drug. Resistant field isolates were rare. Due to the increasing use of amantadine/rimantadine in Taiwan, continued surveillance for amantadine/rimantadine-resistant influenza A viruses is warranted.