WHO officials say blood samples from a 16-year-old Egyptian girl and her uncle who died in December show that the virus was resistant to Tamiflu.
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Both patients were treated with the drug.
The U.N. agency says the drug resistant form of the virus is not widespread. WHO officials say they are not changing their recommendation to treat with Tamiflu, known generically as Oseltamivir.
The agency also says the mutated virus found in the two Egyptians did not have an ability to pass from human to human.
Scientists are afraid that the H5N1 deadly strain of the flu will mutate into a form easily passed among humans, sparking a global pandemic.
Most bird flu patients have been infected by direct contact with sick birds.
The two Egyptians, and another relative who also died in December, lived in close contact with poultry at their home in the Nile Delta.
Ten Egyptians have died from bird flu.
Some information for this report was provided by AFP, AP and Reuters.