Flu thumbs nose at a virus-fighting drug

The dominant strain of flu in the United States this season is mostly resistant to the leading anti-viral drug Tamiflu, and scientists and health officials are trying to figure out why.

The problem is not yet a public health crisis because this has been a below-average flu season so far, and because the Tamiflu-resistant strain, one of three circulating, is still susceptible to other drugs. But infectious disease specialists are worried nonetheless.

Last winter, about 11 percent of the throat swabs from patients with the most common type of flu that were sent to the Centers for Disease Control and Prevention for genetic typing showed a Tamiflu-resistant strain. This season, 99 percent do.

"It's quite shocking," said Dr. Kent A. Sepkowitz, director of infection control at Memorial Sloan-Kettering Cancer Center in New York. "We've never lost an anti-microbial this fast. It blew me away."

The single mutation that creates Tamiflu resistance appears to be spontaneous, and not a reaction to overuse of the drug. It might have occurred in Asia, and it was widespread in Europe last year.

In response, the disease control agency issued new guidelines two weeks ago. It urged doctors to test suspected flu cases as quickly as possible to see if they are caused by the resistant strain.

The Tamiflu-resistant strain is called H1N1. Its resistance mutation could fade out, an agency scientist said, or a different flu strain could overtake H1N1 in importance, but right now it is causing almost all flu cases in the country, except in a few Western states.

Complicating the problem, anti-viral drugs work only if they are taken within the first 48 hours of infection. A patient with severe flu could be given the wrong drug and die of pneumonia before test results come in. So the new guidelines suggest that doctors check with their state health departments to see which strains are most common locally and treat for them.

"We're a fancy hospital, and we can't even do the A versus B test in a timely fashion," Sepkowitz said. "I have no idea what a doctor in an unfancy office without that lab backup can do."

If a Tamiflu-resistant strain is suspected, the disease control agency suggests using a similar drug, Relenza. But Relenza is harder to take; it is a powder that must be inhaled and can cause lung spasms, and it is not recommended for children under 7.

Relenza, made by GlaxoSmithKline, is known generically as zanamivir. Tamiflu, made by Roche, is known generically as oseltamivir.

Alternatively, patients who have trouble inhaling Relenza can take a mixture of Tamiflu and rimantadine, an older generic drug that the agency stopped recommending two years ago because so many flu strains were resistant to it. By chance, the new Tamiflu-resistant H1N1 strain is not.

"The bottom line is that we should have more antiviral drugs," said Dr. Arnold S. Monto, a flu expert at the University of Michigan's School of Public Health. "And we should be looking into multidrug combinations."