Flu now resists two key drugs

Published: Sunday, January 15, 2006 at 6:01 a.m.
Last Modified: Sunday, January 15, 2006 at 12:00 a.m.
ATLANTA - The main influenza strain circulating in the United States has abruptly become resistant to two of the four drugs used to treat it, the Centers for Disease Control and Prevention said Saturday in a rare weekend news conference warning doctors not to use the drugs because they will not work.
The startling discovery could leave flu patients who are at high risk of severe illness or death dependent on another drug, Tamiflu, that is already in short supply around the world because it is the main weapon against bird flu.
But there is no guarantee that Tamiflu will remain a reliable weapon: There have already been reports from Asia of flu viruses with resistance to that drug as well.
The two already ineffective drugs, amantadine and rimantadine (trade names Symmetrel and Flumadine), are among the few pharmaceuticals prescribed to cut short a flu attack and reduce its symptoms, making the disease less dangerous for the elderly and those with compromised immune systems.
But this flu season, 91 percent of samples of the main flu virus circulating in the United States, known as H3N2, that were tested by the CDC have shown resistance to the two drugs, the CDC's director, Dr. Julie Gerberding, said Saturday.
The proportion of viruses resistant to the two drugs was 11 percent last year and less than 2 percent 2 years ago, Gerberding said.
"I don't think we were expecting the increase to be quite as dramatic so soon," she said.
Gerberding gave two possible hypotheses for the sharp increase: a mutation in the flu virus in the United States, or importation of a virus that had already gained resistance, possibly from Asian countries where the drugs are sold over the counter.
Concerns have been growing about resistance to the two drugs, which prevent the flu virus from attaching to cells and releasing genetic material in order to begin reproducing.
In a paper published by The Lancet in September, CDC flu researchers reported that viral samples sent to the World Health Organization from countries around the world showed "an alarming increase" in resistance to the drugs during the past 10 years.
The CDC could not say Saturday how much amantadine and rimantadine, which are collectively called adamantanes, are used in the United States each year.
The drugs, which came onto the market in 1966 and 1993, respectively, are being slowly replaced by two newer drugs, oseltamivir (the generic name for Tamiflu) and zanamivir (Relenza). The newer drugs attack not only influenza A - the family of strains that includes both H3N2 and the bird flu virus, H5N1, and is the only one that causes wide epidemics - but also the less common influenza B that also circulates in the United States, Gerberding said.
"Everything we have tested this year at CDC is susceptible to Tamiflu and Relenza," she said.
Flu experts reached Saturday said it is difficult to predict the effect of losing half of their ammunition against flu. Each year in the United States, more than 36,000 people die from flu complications.
"The advantage of the adamantanes is they were cheaper and there was a lot more clinical experience with them," said Dr. Walter Orenstein, associate director of the Emory Vaccine Center, who was formerly the CDC's chief immunization official.
"It limits the options that we have with regard to treatment of people who might be at particularly severe risk of complications," he said.
The adamantanes cannot be used against avian flu H5N1, which has sickened 148 people and killed 79 in the three years since it began moving west from Southeast Asia. That virus is already resistant to adamantanes, possibly because some countries gave the drugs to poultry flocks.
Tamiflu is the main pharmaceutical weapon against common flu strains as well as avian flu H5N1 and is in high demand around the globe because it is made by a single manufacturer and currently in a single plant. There have been reports of hoarding and stockpiling in several countries.
The United States has placed orders for a national stockpile of Tamiflu with the manufacturer, Roche Inc., but other national governments ordered earlier and it is believed the U.S. order may take a while to be filled.
And Tamiflu has already proved not to be an effective weapon against flu.
Last month , scientists from Hong Kong and Vietnam said in the New England Journal of Medicine that two of eight patients infected with avian flu H5N1 died despite treatment with Tamiflu. The virus in both patients had mutated in a way that made the drug ineffective. An earlier paper described another Vietnamese patient who recovered from a flu virus that had become partially resistant to Tamiflu.

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