A mutation of the Influenza A viruses (H1N1 subtype) known to be resistant to Oseltamivir (marketed as Tamiflu®)  accounted for an estimated 19% of circulating influenza viruses in the United States during the 2007-2008 flu season, , according to a study published in the March 11 issue of JAMA, which is being released early online because of its public health importance. This is the first time the strain has been detected.

"Before the 2007-2008 influenza season, detection of oseltamivir-resistant viruses in humans had typically been reported only among persons treated with oseltamivir," lead investigator Nila J. Dharan, MD, of the Centers for Disease Control and Prevention, Atlanta, and colleagues wrote of the research. They add, "Human-to-human transmission of an neuraminidase inhibitor-resistant virus had never been documented." The drug resistance seemed to be unrelated to oseltamivir use, and caused illness similar to oseltamivir-susceptible A(H1N1) viruses.

For the research, Dharan’s team examined the trends and characteristics of patients infected with oseltamivir-resistant and -susceptible influenza A(H1N1) virus. Among 1155 influenza A(H1N1) viruses tested from 45 states, 12.3% (from 24 states) were resistant to oseltamivir. Among the resistant cases, the patient’s median age was 19 years; five patients were hospitalized, and four died. None of the patients reported oseltamivir exposure before influenza diagnostic sample collection.

“The emergence of oseltamivir resistance has highlighted the need for the development of new antiviral drugs and rapid diagnostic tests that determine viral subtype or resistance, as well as improved representativeness and timeliness of national influenza surveillance for antiviral resistance,” caution the authors.

Investigators also point out that the study’s small sample size demands careful interpretation of the findings and should not be used to extrapolate about the frequency of this complication in hospital settings.

Still, they write, "Early identification and prolonged isolation precautions appear prudent in the care for infected immunocompromised patients to prevent [hospital] influenza virus outbreaks. This study confirmed that circulating H274Y-mutated A(H1N1) viruses can retain significant pathogenicity and lethality, as shown in these elderly or immunocompromised patients with lymphocytopenia, underlining the urgency for the introduction of new effective antiviral agents and therapeutic strategies."

The team predicts this year’s flu season will see continued prevalence of the oseltamivir-resistant A(H1N1) virus, with increased resistance to the drug. Preliminary data identifies resistance to oseltamivir among 98.5% of the influenza A(H1N1) viruses tested.

In response, the CDC released Interim Antiviral Guidance for 2008-09 <http://www.cdc.gov/flu/professionals/antivirals> for the use of influenza antiviral medications, including recommendations for clinicians to consider the results of patient testing and local influenza surveillance data on circulating types and subtypes of influenza viruses in deciding whether oseltamivir alone could be used.

"These guidelines provide options, including preferential use of zanamivir or a combination of oseltamivir and rimantadine, which might be more appropriate in treating patients who might have influenza caused by an oseltamivirresistant virus," Dharan and colleagues write.