The H7N9 virus became resistant to Tamiflu in three out of 14 patients treated with antiviral drugs at Shanghai Public Health Clinical Centre, BBC News reported.
The researchers, writing in the Lancet, said resistance emerged with "apparent ease" and was "concerning".
Doctors analysed the virus in 14 patients. All had pneumonia and half needed ventilation to keep them alive.
Treatment with antivirals reduced levels of H7N9 in most patients and led to an improvement in symptoms.
However, the treatment failed in three patients. Genetic testing of the virus in these patients showed it had acquired the mutations needed to resist the drugs.
The doctors believe that in at least one patient the emergence of resistance was a direct consequence of treatment with Tamiflu.
Such antiviral drugs are the only way of treating the infection.
"The apparent ease with which antiviral resistance emerges in H7N9 viruses is concerning, it needs to be closely monitored and considered in future pandemic response plans," researchers said.
There have been 131 confirmed cases and 36 deaths in China since the virus was first reported early this year.
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