NEW YORK (Reuters Health) Feb 02 - Approximately 90% of influenza A virus isolates circulating in the US in this flu season are resistant to the adamantane drugs amantadine and rimantadine, report investigators at the Centers for Disease Control and Prevention in Atlanta.

"Our results indicate that these drugs should not be used for the treatment or prophylaxis of influenza in the United States until susceptibility to adamantanes has been re-established among circulating influenza A isolates," lead author Dr. Rick A. Bright and his associates advise.

According to their report in the Journal of the American Medical Association published online on February 2nd, the frequency of resistance increased from 1.9% in early 2004 to 11% during the 2004-2005 season.

They obtained influenza isolates collected from 26 US states between October 1 through December 31, 2005. They used pyrosequencing to determine DNA sequences of the viral M2 ion channel protein gene, which, when bound to an adamantane drug, prevents virus replication within the infected cell. The S31N drug resistance mutation of the M2 gene confers resistance to the adamantanes.

The results showed that 92.3% of 290 influenza A(H3N2) and 25% of 8 influenza A(H1N1) had mutations in M2 conferring adamantane resistance. Moreover, 10 of 10 H3N2 isolates submitted from Mexico and three of three from Canada also contained the drug resistance mutation in M2.

Conventional sequencing and biological assays on representative samples confirmed these results. The authors note that similar increases in adamantane resistance have been reported in Asia.

"It is most likely that patients were infected by H3N2 viruses circulating in the community already containing the S31N drug-resistant mutation in the M2 protein," Dr. Bright´s group theorizes.

In a related editorial, Dr. David M. Weinstock and Dr. Gianna Zuccotti, from Memorial Sloan-Kettering Cancer Center in New York, comment that adamantane resistance was observed in Asia as early as 1997, and increased markedly thereafter, a phenomenon that they attribute to the availability of over-the-counter amantadine and rimantadine.

Moreover, fears of an avian influenza pandemic have led to inappropriate use of adamantane drugs among humans and to treat poultry and livestock in Asia. They point out that resistance to the other class of influenza antiviral agents, neuraminidase inhibitors, is also beginning to show up in Japan.

Dr. Weinstock and Zuccotti advise that "the response (to increased antiviral resistance) must be global and immediate." Among their recommendations are education for patients and communities, prevention of the release of over-the-counter antiviral drugs, and recognition that fears of an avian influenza pandemic may be fueling the drastic increase in resistance.

However, there is hope, they add, that if antiviral use is curtailed, susceptible strains may reemerge so that the drugs could regain their utility against epidemic and pandemic influenza.