Virtually all samples of seasonal influenza virus tested by the U.S. government this year were resistant to adamantanes, the class of drugs considered to be the leading treatment for flu infection, a new report shows.

This means that the drugs in this class, amantadine and rimantadine, are ineffectual and shouldn't be used, health experts said.

"We were absolutely shocked at the findings," said Rick A. Bright, an immunologist at the U.S. Centers for Disease Control and Prevention. "This renders this class of drugs useless for influenza for now and for the foreseeable future. We don't expect this to go away any time soon, especially as other countries use it in over-the-counter formulations."

Others said the news was not so shocking, given the propensity of bacteria to develop resistance to antibiotics. "We see emerging resistance to antibiotics, so it's not surprising to see viral resistance," said Dr. Len Horovitz, a pulmonary specialist at Lenox Hill Hospital in New York City.

The findings, from the Journal of the American Medical Association, were released Thursday because of their public health significance. They will also appear in the Feb. 22 print issue of the journal.

Amantadine and rimantadine have been used for years against community outbreaks of influenza A. They are also included in the national stockpile to guard against a possible influenza pandemic.

Flu outbreaks continue to be a major public health concern. According to the study, 10 percent to 15 percent of the U.S. population come down with the flu every year, and about 31,000 people die of it. Vaccination is considered the best strategy to prevent infection.

On Jan. 14, the CDC issued a Health Alert recommending that amantadine and rimantadine not be used to treat or prevent influenza A infections in the United States for the remainder of this flu season. The alert was issued because 91 percent of the 120 influenza A virus samples that were tested were resistant to these two drugs.

"We put the alert out the day after we had the 91 percent figure," Bright said.

The current study expands and updates that testing. A total of 209 influenza isolates (including the original 120) from 26 states across the United States were collected and analyzed. Overall resistance was 92 percent.

Ten isolates from Mexico were all resistant. An earlier study in The Lancet showed a 96 percent resistance in China, Bright added.

The speed at which the resistance developed was the most surprising to health officials. "It's very rare we see such a rapid increase," Bright said. "We did not expect to see over 90 percent."

Researchers suspect it has to do with widespread, over-the-counter and unregulated use of the drugs in other countries. "We believe that it occurred due to pressure from people overusing this class of drugs," Bright said.

But the resistance is likely to stay for the foreseeable future and possibly longer. "Until every place in the world stops using this medication, it may never go away. It may be useless forever," Bright stated.

Both amantadine and rimantadine should stay in the national stockpile, Rick said, as they might still be of use in an emergency situation.

Tamiflu (oseltamivir) and Relenza (zanamivir), antiviral drugs which belong to the neuraminidase inhibitor class of antivirals, still have some use, although their effectiveness is unknown if it comes down to a full blown flu outbreak or pandemic.

"So far, they're still OK but we're concerned that people will be using them more and might begin using them inappropriately and, with increased and inappropriate use, we do expect to see an increase in resistance," Bright said.

Tamiflu and Relenza are also included in the stockpile but, according to a study released earlier this month, are probably not enough on their own to counter an outbreak or pandemic.

More energy and resources need to be devoted to developing new antiviral drugs, surveillance needs to continue, and people need to get vaccinated, Bright said.

But a recent report released from the CDC found that influenza vaccination rates for U.S. children aged 6-23 months were low in the 2003-04 flu season.

"When you rely on any antiviral drug, you're always a single mutation away from resistance," Bright said.

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