EMPIRICAL ANTIVIRAL TERATMENT FOR PERSON WITH SUSPECTED INFLUENZA

October 20, 2009 — On October 16, the US Centers for Disease Control and Prevention (CDC) issued interim guidelines for chemoprophylaxis and early empiric antiviral treatment in persons with suspected influenza, including 2009 H1N1 influenza infection and seasonal influenza.

The new interim recommendations, which update those from September 22, 2009, aim to assist clinicians during the 2009-2010 influenza season in prioritizing use of antiviral medications for hospitalized patients and those at higher risk for complications from influenza. The CDC notes that the recommendations can be modified as indicated by local epidemiologic data, patterns of antiviral susceptibility, antiviral supply considerations, or observed changes in the clinical presentation or antiviral susceptibility of 2009 H1N1 influenza. These guidelines should be considered interim recommendations and will be updated as needed.

"As of October 3, 2009, 99% of circulating influenza viruses in the United States were 2009 H1N1 influenza (previously referred to as novel influenza A [H1N1])," the guidelines authors write. "Among people who become infected with 2009 H1N1, certain groups appear to be at increased risk of complications and may benefit most from early treatment with antiviral medications. Based on currently available data, approximately 70% of persons hospitalized with 2009 H1N1 influenza have had a recognized high risk condition."

High-risk groups include children younger than 2 years, adults 65 years or older, and pregnant women and those up to 2 weeks after delivery or miscarriage. In addition, persons at high-risk include those with immunosuppression; disorders compromising respiratory tract function or handling of respiratory secretions or increasing risk for aspiration; or chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematologic (including sickle cell disease), or metabolic diseases (including diabetes mellitus).

Updated Guidelines

Updates since the September 22, 2009, guidelines include the following:

• The guidelines authors elucidate considerations for treatment and chemoprophylaxis in persons vaccinated with the 2009 H1N1 and seasonal influenza vaccines.
• In addition to pregnant women, those up to 2 weeks postpartum or after a miscarriage are now included as being at increased risk for complications from 2009 H1N1 influenza.
• For children younger than 1 year, additional oseltamivir dosing instructions are given.
• Adverse events and contraindications associated with use of oseltamivir and zanamivir are reviewed.

The guidelines note that antiviral medications can decrease the severity and duration of influenza illness and can lower the risk for severe illness, mortality, and other complications. Treatment or prophylaxis with antiviral medications is not necessary for most healthy individuals with an illness consistent with uncomplicated influenza or for those who appear to be recovering from influenza. Severe symptoms, including evidence of lower respiratory tract infection or clinical deterioration, in persons of any age or previous health status presenting with suspected influenza should mandate prompt empiric antiviral therapy.

All persons hospitalized for suspected or confirmed influenza should be treated with oseltamivir or zanamivir. Persons with suspected or confirmed influenza who are at higher risk for complications, described in the fourth paragraph, should be considered for early empiric treatment with oseltamivir or zanamivir.

Compared with older children and adults, children aged 2 to 4 years are more likely to need hospitalization or urgent medical evaluation for influenza. However, the risk is still much lower vs children younger than 2 years, and antiviral treatment is not necessarily needed for children aged 2 to 4 years with mild illness and without high-risk conditions.

When antiviral treatment is indicated, it should be started as soon as possible because maximal benefits ensue when patients begin treatment within the first 2 days of illness, although some studies of patients hospitalized for seasonal and 2009 H1N1 influenza have shown possible benefit of antiviral therapy started later than 48 hours after symptom onset.

Measures to minimize delays in starting treatment may include educating individuals who are at higher risk for influenza complications of the signs and symptoms of influenza and the need for early treatment as soon as possible after onset of influenza symptoms such as fever or respiratory tract symptoms. In addition, these patients and those who report severe illness should have rapid access to telephone consultation and clinical evaluation. Empiric treatment based on telephone contact may be considered for patients at higher risk for influenza complications, if hospitalization is not needed, and if this will result in markedly less delay before treatment is started.

Because a negative rapid test result for influenza does not rule out influenza, treatment should not be delayed pending laboratory confirmation of influenza. Sensitivity of rapid tests ranges from 10% to 70% for detection of 2009 H1N1.

In accordance with guidelines from local and state health departments, real-time reverse transcriptase-polymerase chain reaction testing for 2009 H1N1 influenza infection should be prioritized for individuals with suspected or confirmed influenza requiring hospitalization.

Consideration for antiviral chemoprophylaxis should usually be limited to individuals at greater risk for influenza-related complications who have been exposed to someone likely to have been infected with influenza. After a suspected exposure, however, early treatment may be an option preferred vs chemoprophylaxis.

Those persons at high risk who are household or close contacts of confirmed or suspected influenza cases can be educated regarding the early signs and symptoms, and if these develop, they can be instructed to contact their healthcare provider immediately for evaluation and possible early treatment. When vaccinated persons have a suspected exposure, early recognition of illness and treatment when indicated are preferred vs chemoprophylaxis.

Circulating Viruses

In the 2009-2010 influenza season, the most common influenza viruses among those circulating are likely to be 2009 H1N1 influenza viruses, especially in younger age groups, but circulation of seasonal influenza viruses is also anticipated. These predictions are based on global experience to date, but the timing and intensity of seasonal influenza virus vs 2009 H1N1 circulation may not be accurately predicted in advance.

The 2009 H1N1 viruses now circulating are susceptible to oseltamivir and zanamivir but are resistant to amantadine and rimantadine. Based on new antiviral resistance or viral surveillance data, however, recommended antiviral treatment regimens may change accordingly. The updated guidelines contain information on the dose and dosing schedule for oseltamivir and zanamivir. The emergency use of oseltamivir in children younger than 1 year is reviewed in an April 2009 Emergency Authorization.