Antiviral resistance eliminates drug from flu arsenal

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Antiviral resistance eliminates drug from flu arsenal

Alternatives to oseltamivir are recommended in CDC guidelines for

treating influenza.

By J. Landers, AMNews staff. Posted Feb. 23, 2009.

Washington -- It's fortunate that the current flu season has been

relatively mild, because physicians have lost one of their prime

weapons against the disease. The dominant strain of flu circulating

this season has become resistant to the antiviral Tamiflu, or oseltamivir.

This newly noted resistance has raised concerns, because oseltamivir

is the most commonly used drug for treating patients who are seriously

ill with influenza. It also is being stockpiled by the federal

government for use in the event of a pandemic flu outbreak.

The antiviral's failure to be beneficial has made prevention even more

important, noted several infectious diseases specialists meeting in

Washington, D.C., for a seasonal and pandemic influenza symposium Feb.

2-3. Their message: Don't stop immunizing patients.

The meeting was organized by the Infectious Diseases Society of

America and was supported by grants from pharmaceutical firms Gilead,

MedImmune and Roche, which manufactures Tamiflu.

About 98% of the A(H1N1) virus, which is currently circulating in the

U.S., is resistant to oseltamivir, said Whitley, MD, professor

of pediatrics, microbiology, medicine and neurosurgery at the

University of Alabama at Birmingham. Dr. Whitley was a co-chair of the

meeting and is president-elect of IDSA.

98% of A(H1N1) flu virus is resistant to oseltamivir.

The virus still can be fought with a second antiviral treatment,

Relenza, or zanamivir, although that medication is inhaled and can't

be used for very young children or for those prone to wheezing.

Oseltamivir is taken orally.

" We've seen antiviral resistance emerge over the past two years, " said

, PhD, director of the Centers for Disease Control and

Prevention's Influenza Division. " Physicians need to be aware that

these viruses are circulating and that Tamiflu may not be effective.

They need to understand that there are other drugs and drug

combinations that may be available. "

The extent of the resistance this season led the CDC in December to

issue interim recommendations directing physicians to use a

combination of oseltamivir and a second antiviral, rimantadine, which

is marketed as Flumadine, when treating influenza. Zanamivir is also

an appropriate choice, the CDC said.

In the United States, four antivirals are approved for treatment of

the flu: oseltamivir and zanamivir, which are neuraminidase

inhibitors, and amantadine and rimantadine, which are adamantanes and

are older drugs.

Why the resistance developed was a matter of debate at the symposium.

Widespread resistance first had been seen last season in Norway, where

20% to 25% of influenza isolates were determined to be resistant. By

last summer virtually all of the H1N1 strains that were circulating in

South Africa were resistant to oseltamivir, Dr. Whitley said. " We are

beginning to see the same thing in the United States. "

The resistance is thought to have resulted from a spontaneous mutation

by the virus rather than as a product of medication overuse.

Antivirals were used infrequently in Norway where resistance was high

but were heavily used in Japan where resistance was low, Dr. Whitley said.

Meanwhile, Roche acknowledged the CDC recommendations and noted

resistance to the medication has historically been low and is

continually monitored. Results from global surveillance studies

indicated that the prevalence of Tamiflu-resistant viruses was less

than 1% between 1999-2007, said the company in a statement.

Few options available

The resistance issue spotlights two additional problems, said

Duchin, MD, chief of the communicable disease epidemiology and

immunization section at the Seattle-King County Dept. of Public Health

in Washington. " It illustrates that we don't have many good options

for the treatment of influenza, which is a common serious disease. "

" We've lost the preferred drug for one of the most common strains of

flu and the strain that is most likely to cause complications, " he

noted. " To have so few drugs is not a good option. "

In addition, physicians have also been " nihilistic about treating

influenza, " he added. " Flu has been undertreated for a long time. "

But there should be opportunities remaining to treat influenza. The

CDC was reporting increasing flu activity in the nation as of the end

of January, with five states -- Colorado, Delaware, New York, Texas

and Virginia -- registering widespread influenza and 21 states,

registering regional activity. One influenza-related pediatric death

had been reported.

http://www.ama-assn.org/amednews/2009/02/23/hlsc0223.htm