Amantadine resistance in clinical influenza A (H3N2) and (H1N1) virus isolates.

Thirty-nine influenza A (H1N1) and (H3N2) virus isolates were examined for their susceptibility to amantadine in allantois-on-shell (AOS) cultures. A range of susceptibilities was found when isolates were titrated in the presence of 2.5 mg/l amantadine. Further titration of resistant isolates at 25 mg/l revealed one isolate which remained totally resistant at this higher concentration. A series of cloned viruses was derived from this resistant isolate, and one other partially resistant isolate, by limiting dilution AOS passage in the absence of amantadine. When these were titrated in the presence of 25 mg/l amantadine, a heterogeneity of amantadine-resistance phenotypes was observed in both sets of virus clones. Finally, chronological ordering of clinical isolates and reference strains tested in this study suggests a higher incidence of amantadine resistance amongst more recent influenza A virus isolates.