Oseltamivir Cuts Mortality Rates Among Certain Flu Patients in ICU

Theodore Lytras, MD, PhD

Critically ill patients with influenza type A(H3N2) have a 30% reduction in mortality rates when they receive oseltamivir within the first 48 hours of the onset of symptoms, according to new research. The findings begin to bring clarity to questions around the impact of early influenza intervention.

A team of investigators from across Europe wanted to add to the existing literature regarding early treatment of neuraminidase inhibitors, which they said has thus far been inconclusive and focused only on influenza A(H1N1)pdm09. They wanted to see what impact early treatment with oseltamivir would have on mortality across all types of the flu.

To find out, they used 8 flu seasons’ worth of data (from the 2010-2011 flu season through the 2017-2018 flu season) from Greek hospitals, focusing on adults admitted to intensive care units with laboratory-confirmed influenza and subsequently treated with oseltamivir.

Patients with A(H3N2) influenza had a significantly lower mortality rate when oseltamivir therapy was initiated within 2 days of the onset of symptoms, compared to those who received later treatment with the therapy. There was no association between early treatment and mortality for patients with other types of the flu, including A(H1N1) and B types.

“I personally expected to find little to no efficacy of early oseltamivir in this very ill population, given our rigorous design and methodology,” corresponding author Theodore Lytras, MD, PhD, of the Hellenistic Centre for Disease Control and Prevention, told MD Magazine®.

Lytras’ instincts proved correct for most types of the flu, he noted, but not for A(H3N2). “The large effect among A(H3N2) patients was surprising, and it is very important for clinicians and patients,” he said.

Lytras added that the study’s competing risk analysis aligns well with oseltamivir’s mechanism of action, which inhibits viral neuraminidase and viral replication, allowing for faster viral clearance and faster recovery. This alignment with the existing understanding of oseltamivir, “raises our confidence in these findings,” Lytras said.

Still, though Lytras conceded that the 30% decrease in mortality is statistically striking, he cautioned that his study isn’t sufficient to draw concrete conclusions about oseltamivir.

“We would not describe the results of our study—or any single study, no matter how well-designed and analyzed—as a basis for ‘firm conclusions,’” he said. “[W]e believe our results will need to be replicated in further studies, ideally randomized.”

In the meantime, Lytras said the findings support the recommendations of the Infectious Disease Society of America.

“Given that treatment must start very close to symptom onset in order to be effective, and given that laboratory confirmation of influenza is not routinely made (therefore patients do not know which influenza type they have), severely ill patients or patients with comorbidities need to start oseltamivir as soon as they exhibit symptoms typical of influenza,” he said.

That holds true for all flu types, at least for now. However, Lytras added that the recommendation is particularly important if A(H3N2) is known to be present in the geographic area.

The study, “Effect of early oseltamivir treatment on mortality in critically ill patients with different types of influenza: a multi-season cohort study,” was published in Clinical Infectious Diseases.