Resistance of Influenza A Virus to Amantadine and Rimantadine: Results of One Decade of Surveillance

Abstract

All clinical isolates of influenza A viruses from patients in Huntington, West Virginia, during the decade 1978–1988 were tested, and 65 of 65 H1N1 and 176 of 181 H3N2 viruses were susceptible to the antiviral action of amantadine and rimantadine. The five resistant viruses were obtained from three members of a family undergoing therapy or prophylaxis with rimantadine. Resistant influenza emerged during treatment with rimantadine and spread to two family contacts, causing typical influenza with fever, myalgia, and cough of 5 days' or less duration. Genetic characterization of the resistant viruses when compared to the susceptible virus isolated on day I from the index case revealed a single amino acid change in the transmembrane portion of the M2 protein. In vitro studies showed that rimantadine was significantly more active than amantadine against both H1N1 and H3N2 viruses. Although this resistant influenza was transmitted and caused illness in one family, the absence of naturally occurring resistant viruses suggests that the emergence of new strains of influenza A each few years may prevent the widespread emergence of resistant influenza A virus.