Infectious Diseases I

Neuraminidase inhibitors continue to be the mainstay of antiviral therapy for recent influenza A

and B strains. These agents inhibit viral neuraminidase, decreasing the release of post-replication

viral particles (virions) from infected cells, limiting spread to additional tissues. Neuraminidase

inhibition may also suppress the initiation of infection after acute inoculation.

Oseltamivir phosphate is an oral (capsule, powder for suspension) ethyl ester prodrug converted

through hepatic ester hydrolysis to the active form oseltamivir carboxylate. Oseltamivir can

be administered to critically ill patients by orogastric or nasogastric tube. An intravenous

formulation of oseltamivir has been tested in early clinical trials. Oseltamivir is the drug of

choice for hospitalized patients with severe influenza.

ii.

Zanamivir is available on the market as an orally inhaled drug delivered by a Diskhaler device.

Intravenous zanamivir was once available for patients with severe influenza through clinical

trial participation or emergency investigational new drug through the manufacturer. However,

this program has been discontinued for countries outside the European Union (internal

communication).

iii.

Peramivir is an intravenous neuraminidase inhibitor with activity against influenza A and

B. Peramivir was approved in December 2014 for use in patients 18 years or older with

acute uncomplicated influenza. Peramivir is administered as a single 15-minute intravenous

infusion. Data are limited for peramivir in critically ill patients.

Adamantanes also interfere with the function of the transmembrane domain of the viral M2

protein, preventing release of viral particles into host cells.

Baloxavir is an endonuclease inhibitor approved by the FDA in 2018 for the management of

uncomplicated influenza in individuals older than 12 years. Baloxavir inhibits endonuclease of

influenza virus A and B strains, limiting the activity of the polymerase acidic protein responsible

for viral gene transcription and virus replication. Data are limited on its safety and efficacy in

patients with severe influenza.

A recent multicenter study together with a systematic review and meta-analysis showed that the use

of corticosteroids in the treatment of influenza was associated with increased hospital mortality in

Susceptibility of influenza to available antiviral agents varies from year to year and between

strains and subtypes. Local surveillance of susceptibility patterns at the beginning and throughout

a respective season is imperative to provide appropriate therapy.

In the past three seasons, close to 100% of tested influenza A (2009 H1N1 and H3) and B

viruses were susceptible to oseltamivir, peramivir, and zanamivir.