Study finds greater, later role for antivirals in flu patients

Nov 14, 2007 (CIDRAP News) – Adults who are hospitalized with serious seasonal influenza infections are more likely to survive if they receive antiviral medications, and older patients may benefit even if treatment is delayed until more than 48 hours after their first symptoms, according to a new study by Canadian researchers.

The standard advice about antiviral treatment for flu—based on previous studies involving relatively young, otherwise healthy adults—is that it must begin within 48 hours after onset of symptoms to be effective. But the new findings, published in the early online Dec 15 edition of Clinical Infectious Diseases (CID), suggest the virus may behave differently in an older, sicker population, giving antiviral medications a role later in the illness course.

The US Centers for Disease Control and Prevention (CDC) classifies people aged 65 and older among the groups vulnerable to serious complications of influenza. In the United States each year, seasonal influenza is linked to about 200,000 hospitalizations and 36,000 deaths, according to a Nov 12 press release from the Infectious Diseases Society of America (IDSA), which publishes CID.

"Influenza causing hospital admission is more common than most people think," said the study's lead author, Allison McGeer, MD, in the IDSA press release. "We will save lives if we recognize and appropriately treat influenza in patients being admitted to the hospital."

The Toronto-based researchers reviewed medical data from 327 adults who were hospitalized for laboratory-confirmed influenza between January 2005 and May 2006 to explore how antiviral medications influenced the patients' treatment outcome. The study was funded by a grant from Hoffman-La Roche, the maker of the antiviral drug oseltamivir (Tamiflu), but the authors state the company had no role in designing, conducting, or reporting the study.

Among the study group, 75% (245) of patients had an underlying chronic illness and 71% (216) had received their annual their annual flu vaccine. The median age of the patients was 77 years (range, 15 to 98).

Thirty-two percent (106) of the patients were prescribed antiviral drugs; three received amantadine and 103 got oseltamivir. Of the 100 patients for whom more detailed oseltamivir treatment data was available, 71 were treated starting more than 48 hours after their flu symptoms began.

The researchers found that antiviral medications reduced the risk of death by 79% (odds ratio, 0.21; 95% confidence interval, 0.06 to 0.80). The treatment did not reduce the length of hospital stay, however.

The finding that antiviral treatment begun more than 48 hours after symptom onset was beneficial for older patients does not contradict other findings that for otherwise healthy adults the drugs are effective only when given sooner, the researchers write. A robust immune response in healthy patients quickly clears the virus from the body, and late antiviral treatment isn't helpful.

"However, patients with severe immunocompromise may not control viral replication for many days, and little is known about the time course of viral load in older patients at risk of influenza complications," the authors report.

They conclude that their findings support the use of antiviral medications in hospitalized patients, but McGeer, in the IDSA press release, said the drugs should be prescribed only when patients really need them. "As with antibiotics, there is a risk for selection for antiviral resistance, and it is important to use the medications only where there is a clear benefit," she said.

Anne Moscona, MD, an antiviral expert at Weill Cornell Medical College in New York City, said the CID study findings have the potential to change how physicians manage flu patients, according to a report today by the Canadian Press (CP). "I think this could be a real advance," Moscona told the CP.

More physicians should be testing for influenza and prescribing antiviral treatment when they find it in hospital patients, she said in the CP report.

The authors of the CID study say the rates of disease they found varied by medical facility and that the number of lab-confirmed flu cases was lower than what they had expected for the number of hospital admissions and population size.

Moscona told the CP, "If we test more, we'll identify more, and people will get more antivirals as opposed to antibiotics."

Frederick Hayden, MD, an antiviral expert with the World Health Organization, told the CP that the study's findings on the benefits of later antiviral treatment were compelling. "It's clear from this experience now that there seems to be a benefit, even with later treatment," he said.

McGeere said her team's findings don't diminish the importance of flu vaccination. "Considerable morbidity and mortality due to influenza remain. We need—and people are working on—better vaccines," McGeer said. "Until we get them, we can help people by diagnosing and treating disease."

McGeer A, Green KA, Pleveshi A, et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis 2007;45(15 Dec) [Full text]

See also:

CDC information on seasonal influenza
http://www.cdc.gov/flu/about/disease.htm

CDC information on antiviral treatment for flu
http://www.cdc.gov/flu/professionals/antivirals/index.htm

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