Senior author Daniel Janies of Ohio State University said the results should serve as a warning to those who consider Tamiflu the next great anti-viral medication.
Stockpiling Tamiflu has become a standard part of many government, business and health organization plans to prepare for a long-feared pandemic flu outbreak, especially in the event that avian flu mutates enough to infect and be easily transmitted among humans, Janies said.
"We can't necessarily say what we've seen in adamantanes is predictive of what will happen with Tamiflu, but in the larger dynamic, perhaps it serves as a cautionary tale," Janies said in a statement.
"Fighting infection is an arms race, and if we're not smart about how we use our arms and understand the evolutionary implications, then we will have ongoing and accelerating problems with drug-resistant microorganisms."
Janies and colleagues analyzed hundreds of avian flu genomes isolated from avian, feline and human hosts from 1996 to 2007.
The study, published in the journal Infection, Genetics and Evolution, found that about one-third of those samples carried mutations enabling the virus strains to resist the effects of adamantane drugs.