Target groups for therapy
●Given the concerning trends of increasing resistance with both the adamantanes and the neuraminidase inhibitors, the risk of promoting antiviral drug resistance should be considered when deciding which patients to treat. Individuals with severe disease (requiring hospitalization or evidence of lower respiratory tract infection) or at high risk for complications should receive antiviral therapy.
●When indicated, antiviral therapy should be initiated as soon as possible since antiviral therapy is most likely to provide benefit when initiated within the first 48 hours of illness. Treatment should not be delayed while awaiting the results of diagnostic testing, nor should it be withheld in patients with indications for therapy who present >48 hours after the onset of symptoms, particularly among patients requiring hospitalization. Furthermore, patients who have a negative rapid antigen test for influenza but in whom the clinical suspicion for influenza infection is high should be treated with antivirals since the sensitivity of these tests may be low.
●We recommend antiviral therapy (with zanamivir or oseltamivir) for all individuals with confirmed or suspected influenza virus infection who are severely ill, such as those with lower respiratory tract infection (eg, dyspnea, tachypnea, unexplained oxygen desaturation), and those who are showing signs of rapid clinical deterioration; we recommend treatment for such patients whether they present early in the course of infection (<48 hours after symptom onset) (Grade 1B) or later (Grade 1C).
●We recommend antiviral therapy for outpatients who present within 48 hours of symptom onset with confirmed or suspected influenza infection and who are at increased risk for complications (Grade 1A). We also recommend antiviral therapy for outpatients who present >48 hours after symptom onset with confirmed or suspected influenza infection and who are at increased risk for complications provided that they are not yet improving (Grade 1C).
●We suggest antiviral therapy for patients who present within 48 hours of symptom onset with mild illness and who are not at increased risk for complications (Grade 2C). There is high quality evidence for benefit to the individual patient; however, there is only low quality evidence regarding the magnitude of the risk of promoting resistance, which remains a major concern. Additionally, when supplies are limited, antivirals should be reserved for high-risk patients.
●We recommend that patients with uncomplicated influenza who have had more than 48 hours of influenza signs and symptoms not be treated with antivirals (Grade 1B).
●We suggest treating all pregnant women with suspected or confirmed influenza, even those who present >48 hours after onset of symptom onset provided that they are not yet improving (Grade 2C)．
Choice of antiviral agent
●Clinicians should review local or state influenza surveillance data during influenza season to determine which types of influenza (A or B) and subtypes of influenza A (H1N1 or H3N2) are circulating, as well as antiviral resistance patterns.
●A neuraminidase inhibitor (zanamivir or oseltamivir) is the recommended antiviral agent for the treatment of patients with influenza infection． Patients who cannot receive zanamivir or oseltamivir (eg, those who cannot tolerate inhaled or enteral agents) should receive intravenous (IV) peramivir.
●The recommended dose of zanamivir is 10 mg (two inhalations) twice daily; the recommended dose of oseltamivir is 75 mg orally twice daily; the recommended dose of peramivir is 600 mg IV as a single dose. Dosing of oseltamivir and peramivir must be modified in the setting of renal insufficiency. The recommended duration of therapy for zanamivir or oseltamivir is five days.
●Because of the high rates of influenza isolates resistant to adamantanes in the United States and in many other countries, amantadine and rimantadine are not recommended for the treatment of influenza.
Mortality — Some observational studies have found an association between oseltamivir use and mortality reduction in patients with influenza . No randomized trials have assessed mortality because all trials have been conducted in healthy individuals in whom the mortality rate from influenza is very low.
Adverse effects of neuraminidase inhibitors are typically mild, although more serious side effects have been described． Zanamivir can cause bronchospasm and a decline in respiratory function in patients with asthma and other chronic respiratory disorders. As a result, the manufacturer has issued a warning advising particular caution in patients with asthma or chronic obstructive pulmonary disease．
Zanamivir inhalation powder is not recommended for use in nebulizers or mechanical ventilators since the lactose carrier can clog ventilator tubing．
There have been postmarketing reports of self-injury and delirium in patients (primarily children) receiving oseltamivir for treatment of influenza. Most of these reports came from Japan, where the drug is used more commonly than in the United States．However, a subsequent study has not demonstrated a causal association between neuraminidase inhibitors and abnormal behavior.
Oseltamivir can also cause nausea and vomiting， but these side effects have not generally resulted in discontinuation of therapy.
Diarrhea is a common adverse effect reported in patients receiving peramivir． Rare but serious adverse effects associated with peramivir include serious skin or hypersensitivity reactions such as Stevens-Johnson syndrome and erythema multiforme. As with oseltamivir, there have been postmarketing reports from Japan of delirium and abnormal behavior leading to injury in patients with influenza who were receiving peramivir.