In a development that experts call alarming, two bird flu patients in Vietnam died after developing resistance to Tamiflu, the key drug that governments are stockpiling in case of an outbreak.

The experts said the deaths were disturbing because the two girls had received early and aggressive treatment with Tamiflu and had gotten the recommended doses.

The new report suggests that the doses doctors now consider ideal may be too little. Previous reports of resistance involved people who had taken the drug in low doses; inadequate doses of medicine are known to promote resistance by allowing viruses or bacteria to mutate and make a resurgence.

Dr. Anne Moscona, a flu expert at Weill Cornell Medical College in New York City, called the deaths frightening and said they demonstrate the dangers of hoarding drugs.

"People who stockpile will naturally share or take drugs at the wrong dose, and that's really a bad idea," said Moscona, who wrote an accompanying commentary in today's New England Journal of Medicine.

Since 2003, avian flu has killed about 70 people, mostly in Vietnam and Thailand, and nearly all involved close contact with infected birds. Health experts fear the virus could morph into a form that spreads easily between people.

Front-line defense

Tamiflu and another drug, Relenza, are expected to be the front- line defense if that happens, but they must be taken soon after infection to be effective.

Tamiflu, made by Swiss-based Roche Holding AG, is the favored drug because it appears to be effective against all kinds of flu, including bird flu. GlaxoSmithKline's Relenza requires an inhaler and has not been widely tested in people with avian flu.

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