CDC Interim Guidance Responds to Growing Oseltamivir Resistance in Influenza A (H1N1)

The AAFP has adopted CDC interim guidance for physicians on the use of influenza antiviral medications during the 2008-09 influenza season. The agency issued the recommendations because a high proportion of influenza A (H1N1) viruses have been found to be resistant to the antiviral medication oseltamivir.

The CDC said in its weekly flu report released Jan. 10 that since Oct. 1, 2008, 103 H1N1 virus samples collected from 25 states have been tested for resistance to the neuraminidase inhibitors oseltamivir and zanamivir.

None of the viruses tested was resistant to zanamivir, but 101 (98 percent) were resistant to oseltamivir.

According to the CDC interim recommendation, when H1N1 virus infection or exposure is suspected, zanamivir or a combination of oseltamivir and rimantadine "are more appropriate options than oseltamivir alone."

Oseltamivir still can be used when influenza B or influenza A (H3N2) is diagnosed.

The CDC reported that during the 2007-08 flu season, 10.9 percent of influenza A (H1N1) viruses tested in the United States were resistant to oseltamivir. During that season, oseltamivir resistance among viruses in Europe ranged from 0 percent to 70 percent. This pattern of resistance has continued, with some Southern Hemisphere countries reporting during the 2008 season that a majority of influenza A (H1N1) viruses tested were resistant to oseltamivir.

The CDC said that low levels of influenza activity in the United States so far this season have produced only a limited number of available samples and a lack of geographic diversity among the samples tested. Those factors, combined with uncertainty about which influenza virus types or subtypes will predominate during the season, "make it too early to make an accurate determination of the prevalence of influenza viruses resistant to oseltamivir nationally or regionally at this time."

Tony Fiore, M.D., M.P.H., medical officer in the CDC's Influenza Division, said physicians should review local or state influenza virus surveillance data weekly during flu season to determine which types and subtypes of influenza virus are circulating in their communities.

He said physicians also can use rapid antigen tests, which can yield results in as little as 15-30 minutes. Some of these tests can distinguish between influenza A and influenza B, but they do not identify subtypes.

Fiore said that's problematic this season because oseltamivir can be used to treat H3N2, but not H1N1. Furthermore, some tests are not as sensitive in adult patients as they are in children, who shed more viruses. That fact can result in false-negative results for adults, he said.

"Physicians need to use local surveillance data and rapid tests to guide them," Fiore said. "There will be times a physician won't be able to tell what they're dealing with."

Another confounding factor, said Fiore, is the timing of chemoprophylaxis. Antiviral medication is effective only when started within 48 hours of illness onset, and he stressed that the elderly, infants and people with chronic conditions should not delay seeking treatment.

"Most people don't get treated," Fiore said. "People get worse and worse. After three days they come in, and it's too late to treat them."

The bottom line, according to him: "It's going to be complicated treating people for influenza this year."

For that reason, Fiore said, physicians should continue to offer influenza vaccine throughout the entire flu season. This year's influenza vaccine is expected to be effective in preventing or reducing the severity of infection with currently circulating influenza viruses, including oseltamivir-resistant H1N1 viruses.

The H1N1 subtype circulating is similar to the virus used in the vaccine, Fiore said. Although the virus has mutated enough to be resistant to oseltamivir, from an immunological standpoint, it hasn't changed significantly.

"It's a very good match," he said.