The Infectious Diseases Society of America (IDSA) would like to address possible confusion among clinicians created by the publication of a new systematic review of neuraminidase inhibitors (oseltamivir, zanamivir) for influenza in the Cochrane Library and the British Medical Journal . IDSA continues to recommend the use of neuraminidase inhibitors for treatment of influenza. The recent Cochrane Review evaluated published and previously unpublished data from randomized clinical trials (RCTs) largely in healthy outpatients with mild illness [2, 3]. The authors reported a modest reduction of illness duration by early neuraminidase inhibitor (NAI) treatment of uncomplicated influenza-like illness with oral oseltamivir in adults (16.8 hours) and in children (29 hours), and with inhaled zanamivir in adults (14.4 hours). These findings are consistent with previous reviews that have reported a reduction of approximately one day in influenza-like illness duration among outpatients with mild illness by early NAI treatment. Of note, the Cochrane analysis included both influenza virus-infected and non-infected persons with influenza-like illness. Given the specific antiviral activity against influenza viruses of NAIs, this analytic approach underestimates NAI treatment efficacy.
Of particular importance, RCTs of NAI treatment in ambulatory patients with mild illness do not inform clinical practice regarding treatment of patients with severe illness or persons at higher risk for influenza complications. No placebo-controlled RCTs are available for NAI treatment of hospitalized influenza patients. Therefore, evidence from the many observational studies of hospitalized seasonal and pandemic 2009 H1N1 influenza patients should be considered, despite the limitations of observational studies compared to RCTs. These observational studies have consistently reported that NAI treatment of influenza in hospitalized patients reduces severe outcomes, including intensive care unit admission and death, especially when treatment is started within two days of illness onset. These studies have also shown that later initiation of NAI treatment may still provide some clinical benefit. No RCT was powered to evaluate the effect of oseltamivir treatment of outpatients to reduce influenza-associated complications such as hospitalization or lower respiratory tract infections; both outcomes are rare in otherwise healthy individuals but more common in persons at higher risk for complications. Pooled data from RCTs have been used to try to assess the effect of outpatient treatment on subsequent complications. While too few hospitalizations were recorded from available RCTs to assess this outcome, published studies have demonstrated a reduction in clinician diagnosed lower respiratory tract infections requiring antibiotics.
IDSA continues to recommend the use of neuraminidase inhibitors for treatment of influenza, and endorses the CDC statement that current antiviral recommendations for influenza remain unchanged .
Similar recommendations for antiviral therapy are an integral part of the American Academy of Pediatrics annual Policy Statement on Influenza from the Committee on Infectious Diseases .
IDSA recommends that clinicians start antiviral treatment with oral oseltamivir as soon as possible for any hospitalized patient with suspected or confirmed influenza and for any patient with suspected or confirmed influenza who has severe or progressive illness. In the U.S., oral oseltamivir or inhaled zanamivir (approved for treatment from age 7 years) is recommended for any outpatient suspected or confirmed to have influenza who is in a group at higher risk for complications from influenza - children younger than 2 years of age, elderly people, pregnant women, people with certain chronic conditions (e.g., pulmonary, cardiac [excluding hypertension], renal, hepatic, metabolic, hematologic, neurologic, or neuromuscular conditions, immunosuppression, or obese persons with body-mass indices equal to or greater than 40)), nursing home residents, American Indians, and Alaska Natives . When oseltamivir resistance is suspected or confirmed in a seriously ill or immunocompromised influenza patient, intravenous zanamivir is recommended and is available on a compassionate use basis from its manufacturer with FDA approval.
IDSA continues to support research on novel influenza therapeutics, including antivirals and immunotherapy, and stockpiling of antiviral agents for pandemic influenza preparedness. However, available influenza vaccines and antiviral medications are currently our best interventions for prevention and treatment of seasonal influenza. While annual influenza vaccination for all persons aged 6 months and older is recommended in the U.S. and is the best way to prevent influenza, many patients who become symptomatic with influenza virus infection can benefit from antiviral treatment with a neuraminidase inhibitor medication started as soon as possible.
- Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. The Cochrane database of systematic reviews 2014; 4:CD008965.
- Heneghan CJ, Onakpoya I, Thompson MJ, Spencer EA, Jones MA, Jefferson T. Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments, 2014. .
- Jefferson T, Jones MA, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments, 2014.
- Centers for Disease Control and Prevention (CDC). "Have You Heard?" CDC Recommendations for Influenza Antiviral Medications Remain Unchanged, 2014. Available at: http://www.cdc.gov/media/haveyouheard/stories/Influenza_antiviral2.html. Accessed: April 2014.
- Committee on Infectious Disease (COID) American Academy of Pediatrics. Recommendations for prevention and control of influenza in children, 2013-2014. Pediatrics 2013; 132:e1089-104.
- Centers for Disease Control and Prevention (CDC). Influenza Antiviral Medications: Summary for Clinicians (Current for the 2013-14 Influenza Season), 2013.