Efficacy of baloxavir marboxil as a prophylactic against influenza among in-patients and analysis of influenza virus mutations in their isolates at a Japanese hospital during the 2023–2024 flu season

TL;DR

This study shows that baloxavir is effective at preventing influenza in hospitalized patients but notes the presence of a mutation that may reduce its effectiveness.

Contribution

Demonstrates baloxavir's prophylactic efficacy in hospitalized patients and identifies the I38T mutation in influenza isolates.

Findings

None of the 34 patients taking baloxavir developed influenza after contact with infected patients.

Three of 11 patients not taking baloxavir became infected (P = 0.012).

The I38T variant was detected in two H3N2 influenza samples.

Abstract

Baloxavir marboxil (baloxavir) is a new anti-influenza drug that works as a cap-dependent endonuclease inhibitor. It is approved for prophylactic use against influenza in Japan, but there are few reports on this usage in hospitalized in-patients. It reportedly reduces patient susceptibility to influenza through a mechanism involving amino acid substitution.

Between August 2023 and July 2024, we investigated the efficacy of baloxavir as a prophylactic against influenza among in-patients at our hospital who had close contact with patients who were infected with influenza viruses in the same rooms. We also investigated the I38T influenza virus variant to baloxavir through samples taken from patients with the virus at the hospital.

We enrolled a total of 45 in-patients who had close contact with other patients who were confirmed to be infected with influenza in the same room. Among 34 of them who were prescribed baloxavir prophylactically, none developed influenza within 5 days from their last contact with infected patients. Conversely, among the other 11 who did not use baloxavir, three became infected with influenza within 5 days following contact with the infected patient (P = 0.012). In 85 samples taken from the patients with influenza, 25 were H1N1 types and 60 were H3N2. We detected the I38T variant of the cap-dependent endonuclease-baloxavir complex structure in two of the H3N2-type samples. Both of these patients had contracted influenza from their children.

According to our results, Baloxavir represents an effective prophylactic against influenza for hospitalized in-patients. However, patients with genetic mutations related to decreased susceptibility to influenza, such as I38T variant, should nevertheless exercise higher levels of caution—particularly around children.

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