Optimizing antiviral therapy for influenza: understanding the evidence

Abstract

Influenza is an important cause of annual epidemics of respiratory viral infection associated with significant morbidity and mortality. Three classes of drugs, the M2 ion channel, neuraminidase and RNA-dependent RNA polymerase inhibitors, are approved for the prevention and treatment of influenza. Due to widespread resistance to the class, the M2 ion channel inhibitors are not recommended currently for therapy. The only polymerase inhibitor, favipiravir, is approved only in Japan and its use is highly restricted. Despite significant data to support the early use of the neuraminidase inhibitors, their use in all patient populations is suboptimal. The data to support the early use of neuraminidase inhibitors will be reviewed, as will current data on the utilization rates in ambulatory and hospitalized populations.

Keywords:

• antiviral therapy
• influenza
• laninamivir
• neuraminidase inhibitors
• oseltamivir
• peramivir
• zanamivir

Financial & competing interests disclosure

Grant or research support, paid to Northwestern University Feinberg School of Medicine, from Cellex, Crucell, GlaxoSmithKlein, and NexBio. MG Ison is a paid consultant to Chimerix, Crucell, and Genentech/Roche; and a paid member of a Data and Safety Monitor Board for Biota, NexBio, and Vertex. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Among ambulatory adults with proven influenza, only 15% are prescribed antivirals but 30% are prescribed antibiotics.

• Rates of prescribing antivirals among children and high-risk adults with influenza remain low.

• Among adults hospitalized with influenza, a declining percentage of patients are prescribed antivirals, especially within 48 h of hospitalization while most are receiving empiric antibacterial therapy.

• Early antiviral therapy has been associated with shorter time to alleviation of illness and reductions in severity of illness, duration of fever, time to return to normal activity and quantity of shed virus in addition to lower rates of infectious complications, hospitalizations and cardiovascular events in ambulatory adults and children.

• Early antiviral therapy in hospitalized patients has been associated with improved clinical outcomes and reduced mortality; many of the studies have documented positive effects on prescriptions for antibacterial agents, in terms of either total duration or use, as well as reduced duration of hospitalization.

• Use of antibiotics in patients with influenza is of unproven benefit in most patients and may increase the risk of adverse effects, including Clostridium difficile colitis, and may lead to antibacterial resistance emergence.

• Clinicians are more likely to prescribe antivirals for influenza when a test confirms that the patient is infected with influenza.