Packets of Tamiflu tablets are stored in the Swiss Army Pharmacy in Ittigen near Bern August 10, 2009. Credit: Reuters/Ruben Sprich

A swine flu virus infecting a woman in Singapore mutated into a drug-resistant form virtually overnight, doctors reported in a study that they say shows the limitations of using drugs to treat influenza.

While the woman recovered, the mutation developed within 48 hours, rendering the infection increasingly resistant to the effects of Tamiflu, the main drug used to fight flu and which is known generically as oseltamivir.

Our data indicate that oseltamivir resistance developed within two days, Masafumi Inoue of the Agency for Science, Research and Technology in Singapore and colleagues wrote in the Emerging Infectious Diseases journal.

The H1N1 swine flu pandemic is over, but the virus has joined the mix of seasonal influenza viruses.

A distant relative, also called H1N1, developed broad resistance to Tamiflu in 2008, and the drug is now considered useless against it. Tamiflu is made and distributed by Roche and Gilead Sciences.

Researchers know that flu is highly prone to mutation and most strains have evolved resistance against two older flu drugs, amantadine and rimantadine.

When H1N1 broke out in March of 2009, doctors feared it would be worse than it was. In Singapore, patients were often treated right away with Tamiflu.

But doctors were also wary that the virus might mutate, and they watched carefully for one particular genetic mutation, called H275Y, that confers resistance to Tamiflu.

Virus samples from the patient in Singapore showed the mutation 48 hours after she started taking the drug, Inoue and colleagues reported.

Whatever the epidemiologic data exhibit, clinicians should consider resistance when patients do not respond to treatment for pandemic (H1N1) 2009 because H275Y can emerge literally overnight, as the case reported here reminds us, they wrote.

One other flu drug is licensed -- GlaxoSmithKline's and Biota's Relenza, known generically as zanamivir. Like Tamiflu, it is in the class of drugs called neuraminidase inhibitors.

A small biotech called BioCryst is developing a flu drug called peramivir.