Two people infected with avian flu have died despite being treated with Tamiflu, a drug many consider to be the best defence against a flu pandemic, doctors say.

Physicians in Vietnam say they found evidence the H5N1 avian influenza virus can quickly mutate into a form that resists the effects of the frontline drug.

Tests found virus samples taken from two patients showed a substitution in a gene that confers resistance to oseltamivir, the generic name for Tamiflu, the researchers report in Thursday's New England Journal of Medicine.

In all, four of eight patients treated in Vietnam for bird flu died despite use of Tamiflu. In one case, a 13-year-old girl was treated during the first 48 hours, which is considered the best time for the drug to work.

Like all viruses, influenza can become resistant to drugs, so the findings are disappointing but not unexpected to virologists.

The cases don't mean Tamiflu won't work in a pandemic, said Dr. Allison McGeer, an infectious disease specialist in Toronto.

Given resistance concerns, three doctors argue in journal commentaries that family physicians have a public health duty not to write prescriptions for patient stockpiles.

Their reasons are:

* The drug should be saved to treat the ill in a pandemic.* People will be confused about when to take Tamiflu.* Inappropriate use of Tamiflu could cause the virus to become resistant.

Dr. Ross Upshur, a family physician in Toronto, says several of his patients have asked for Tamiflu because of worries about a pandemic.

"I told them that I wasn't going to write a prescription for Tamiflu and I thought that it was unnecessary," Upshur said.

Demand for Tamiflu is growing. Roche Pharmaceuticals has temporarily stopped sales during the regular flu season because the manufacturer is worried about a shortage.

Canada's chief public health officer, Dr. David Butler-Jones, advises against stockpiling the drug for personal use when it becomes available.

"My advice would be generally, no, I don't think it's appropriate at this time," said Butler-Jones. "But the jury is still out, and that advice may change in a year or two."

The latest studies on Tamiflu show it won't be a magic bullet for treatment, and probably works better at preventing infection.

Using it to prevent infection would require much larger stockpiles. Although it will be expensive, governments should be pressed to stockpile more and use it where it will be most effective, McGeer said.

"Everybody in society has the right to say to public health people and governments: it's important to me that when the pandemic comes, that you're going to be adequately protecting me and people I work with and the people I live with," said McGeer. "How are you going to do that?"

If all government stockpiles of Tamiflu were used for prevention during a pandemic, CBC News conservatively estimates, there would be enough to protect two per cent of Canadians, based on the population and how long the drug needs to be taken.