Oseltamivir-resistant influenza viruses prompt search for alternative treatments

Oseltamivir-resistant influenza A viruses, including sporadic isolates of the 2009 pandemic strain, have prompted more research into newer therapies and combinations, according to a speaker at the 2010 Conference on Antimicrobial Resistance.

Frederick Hayden, MD, of the University of Virginia School of Medicine, in Charlottesville, reviewed some of the latest data on oseltamivir resistance, noting several studies in which resistant viruses have been transmitted, even in the absence of drug pressure. Clusters of illnesses, including health care facility outbreaks in the United States and Wales, have led to severe morbidity and mortality in some instances. However, there has been no sustained community spread to date.

So far, about 200 viruses among more than 20,000 pandemic samples have tested positive for oseltamivir-resistance, with evidence of the H275Y mutation in all cases. About half of the oseltamivir-resistant strains were detected in immunocompromised hosts assigned to prolonged therapy. About 15% of patients were failing post-exposure prophylaxis. Most cases were mild and the illnesses were self-limited, but children and the immunocompromised patients were among the most severely affected, Hayden said.

The emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors also indicates that resistance is not limited to influenza A, he said. Resistance in influenza B viruses is troubling, according to a clinician in attendance at the meeting, because of the limited access to alternative treatment options.

A variety of treatment regimens are now being explored as alternatives for treatment in instances of oseltamivir-resistant influenza. Currently, zanamivir (Relenza, GlaxoSmithKline) is an effective alternative choice, Hayden said, preferably in IV formulations for more severe cases.

Additionally, combination antiviral therapies in various phases of clinical trials may soon be available. Hayden cited one study in which a combination of nebulized zanamivir and rimantadine was compared with a combination of saline and rimantadine. Although results suggested some clinical benefit for this combination, Hayden said the data showed limited benefit for treating M2 inhibitor-resistant viruses. – by Melissa Foster

For more information:

• Hayden FG. Influenza Resistance to Antiviral Drugs: Public Health and Management Implications. Presented at: 2010 Annual Conference on Antimicrobial Resistance; Feb. 1-3, 2010; Bethesda, Md.