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Rising concern over flu-drug resistance

March 2, 2009 |  9:51 am

Infectious disease experts are so worried about the rapid rise in resistance to the flu drug Tamiflu -- as we reported in a story last month -- that the Journal of the American Medical Assn. is releasing reports today online in advance of its usual publication dates.

I5natlkf Studies in JAMA today (and a review to be published later this week in the New England Journal of Medicine) report that as of Feb. 19, resistance to oseltamivir, better known as Tamiflu, had been identified in 98.5% of U.S. influenza A(H1N1) viruses tested -- a startling increase over the 2007-2008 flu season, when resistance was detected for the first time in 12% of H1N1 viruses tested.

Each flu season, several types of flu viruses circulate, and various ones can dominate in different regions and times. Only the H1N1 virus is showing signs of Tamiflu resistance, according to the national Centers for Disease Control and Prevention.

What mystifies infectious disease experts and microbiologists is that the Tamiflu-resistant strain now circulating appears to be a mutation that spread naturally, not as a response to antiviral use.

Another surprise is that the resistant virus appears to spread just as easily and to cause disease as readily as nonresistant strains, which is not always the case. This is a particular concern for the hospitalized, the elderly and others whose immune systems are already weakened and who are at especially high risk of developing pneumonia and dying, according to a second JAMA study released online today.

It's common to see a trade-off between resistance and virulence; mutations that cause resistance often come at a cost to the microbe. But that doesn't seem to be the case with Tamiflu resistance in the H1N1 virus, according to both of the JAMA studies.

At a hospital in the Netherlands, five healthcare workers fell ill with the resistant virus after admitting a patient who had it, according to the second study. They may have then spread the virus to three other patients already in the hospital, one elderly and two who had had stem-cell transplants, resulting in three cases of viral pneumonia and two deaths. Although the sample size was small, the study's authors warned of the threat of hospital outbreaks and recommended isolating infected patients.

The CDC issued new guidelines to physicians in December to substitute an alternative drug, Relenza, for Tamiflu or to combine Tamiflu with an older antiviral, rimantadine, if the H1N1 virus is the main strain in circulation in their communities.

In an editorial that accompanies the JAMA studies, Dr. David M. Weinstock of the Dana-Farber Institute in Boston and Dr. Gianna Zuccotti of Brigham and Women's Hospital in Boston, issued an urgent plea for new antiviral therapies as well as new ways to rapidly diagnose viral strains.

Until then, they wrote, "For now, the best tools to mitigate influenza infection are tried-and-true -- vaccination, social distancing, hand washing and common sense."

-- Mary Engel

Photo: Mark Boster