Approach

The main goals of treatment at the patient level are reduction in severity and duration of symptoms and prevention of complications. At a public health level, the aim is to prevent or control outbreaks of influenza to avoid an epidemic or pandemic situation. CDC: influenza (flu) external link opens in a new window

When antiviral treatment is indicated, it should ideally be given within the first 48 hours of suspected or laboratory-confirmed influenza.

Treatment is recommended for people at high risk of developing complications of influenza, and therapy can be started within 48 hours of onset of symptoms. Treatment can be considered for people diagnosed with influenza 48 hours after onset of symptoms, who have continued symptoms.

All patients hospitalised for influenza require antiviral treatment.

People not at high risk of complications may be given antiviral treatment if influenza is highly suspected or confirmed, it is within 48 hours of symptom onset, and they wish to shorten the duration of their illness.

Complications may occur in any patient and it is not always possible to estimate the risk of complications, which makes treatment decisions more difficult; however, a variety of high-risk subgroups are more susceptible. At-risk groups include:[2]

  • Patients with chronic pulmonary (including asthma) or cardiac conditions

  • Patients with diabetes mellitus, renal disease, liver disease, chronic neurological conditions, or immunosuppression

  • Patients in nursing homes or long-term care facilities

  • Children aged <2 years

  • Adults aged ≥65 years

  • Pregnant women.

Antiviral prophylaxis after exposure to an infected individual is reserved for at-risk populations.[109][110]

Uncomplicated influenza infection

Uncomplicated influenza infection is an acute respiratory infection caused by influenza A or B viruses that is usually self-limiting in the general population.[2] Treatment is aimed at supportive care of the symptoms associated with the respiratory tract infection. These treatments usually include antipyretics/analgesics for fever, and increased fluid intake to counter dehydration. The symptoms typically resolve in approximately 1 week; however, cough and fatigue may persist for longer.[111]

Complicated influenza infection

A more severe, complicated illness can occur in influenza infection and is associated more often with influenza A infection rather than influenza B infection.

Complications of upper respiratory tract infection include otitis media and bacterial sinusitis. Complications of lower respiratory tract infection include primary viral pneumonia and secondary bacterial pneumonia.

Treatment of these complications may require more aggressive supportive care, often necessitating hospitalisation, accompanied by antibiotics and/or antiviral treatment.

The highest rates of hospitalisation are in infants, patients aged >65 years, and patients with chronic medical conditions. Over 90% of influenza-related deaths have been in patients aged >65 years.[11]

Antiviral treatment of early influenza infection

The US Centers for Disease Control and Prevention (CDC) recommends antiviral treatment is given as soon as possible for patients with confirmed or suspected influenza who have severe, complicated, or progressive illness, or who require hospitalisation, as well as for patients who are at higher risk for complications.[2][109][112] While antivirals are approved by the US Food and Drug Administration for uncomplicated acute illness, guidelines tend to recommend these drugs for complicated illness as well as for those at risk of complications. Local guidelines may vary and should be consulted.[113]

The neuraminidase inhibitors (zanamivir, oseltamivir, and peramivir) are active against both influenza A and B.[112][114][115][116][117]Oseltamivir and zanamivir have modest effectiveness against the symptoms of influenza in otherwise healthy adults,[118] [ Cochrane Clinical Answers logo ] and have been widely used in the treatment of 2009 influenza A/H1N1.[114][119][120][121] However, there has been extensive debate over the use of oseltamivir and whether it does reduce complications in otherwise healthy adults and children.[114][122][123][124] Findings from meta-analyses show that oseltamivir modestly reduces time to clinical symptom alleviation in adults with influenza, but increases the incidence of nausea and vomiting.[121][125] The effect on mortality and complication rates was uncertain.[121] Observational studies suggest oseltamivir may reduce mortality in hospitalised patients with seasonal influenza.[126]

It has been reported that oral oseltamivir and inhaled zanamivir reduce the duration of influenza illness when started within 48 hours of symptom onset, both in children up to age 12 years and in adults.[109][116][127]The benefits of treatment are greatest when medicines are initiated in the first 24-30 hours of symptom onset.[128][129]

If being prescribed, oseltamivir and zanamivir should be given to patients presenting within 2 days of onset of symptoms and given for 5 days. Peramivir is given in a single infusion, and should also be given within 2 days of symptom onset.[2][109][112]Peramivir may be recommended for those who are unable to take oral or inhaled neuraminidase inhibitors.

Oseltamivir is generally well tolerated in adults but may cause vomiting in children. There is less evidence for zanamivir than with oseltamivir that it reduces respiratory complications in adults.

A drug safety alert relating to oseltamivir was issued in November 2006 following reports of self-injury and delirium associated with its use. The alert states that people with influenza, particularly children, may be at an increased risk of self-injury and confusion shortly after taking oseltamivir and should be closely monitored for signs of unusual behaviour.

Pregnant women presenting with uncomplicated illness due to influenza, and who have no evidence of systemic disease, can be offered either zanamivir or oseltamivir.[109] In view of the lower systemic exposure, zanamivir is recommended as first choice, although either drug can be used. In women who are breastfeeding, oseltamivir is preferred over zanamivir. Children aged <1 year who have symptoms of seasonal influenza should be treated with oseltamivir.[109]

Baloxavir marboxil, a polymerase acidic endonuclease inhibitor, is active against both influenza A and B. The US Food and Drug Administration has approved baloxavir marboxil for the treatment of acute uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours, and who are otherwise healthy or at high risk of developing influenza-related complications.

The M2 inhibitors amantadine and rimantadine are only active against influenza A. [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] There is consensus that rimantadine should not be used as first-line treatment, because cross-resistance to amantadine is high. Due to an increase in resistant isolates, physicians should seek advice from local authorities regarding antivirals based on seasonal resistance patterns.[112]

Post-exposure antiviral chemoprophylaxis

Should be considered for:[109][110]

  • People at high risk of developing complications of influenza if illness develops shortly after influenza vaccination, before an adequate immune response develops.

  • People in whom the vaccine is contraindicated. This may include anaphylaxis to egg or allergy to other components of the vaccine, febrile illness, or history of Guillain-Barre syndrome within 6 weeks of previously administered influenza vaccine.

  • People who have not received the vaccine but present with acute respiratory symptoms during a known influenza outbreak.

  • Unvaccinated people in close contact with those at high risk of developing complications of influenza during an influenza outbreak.

  • All residents of long-term facilities or nursing homes, including those already vaccinated, if an outbreak of influenza occurs in the community where they are living. [ Cochrane Clinical Answers logo ]

  • People who have highest risk of complications, including death. This may include immunocompromised people.

  • People who were unable to receive vaccine due to shortage, if they are at high risk of developing complications of influenza.

Both oseltamivir and zanamivir have been shown to be effective as prophylaxis against infection when given early after exposure to an infected individual. [ Cochrane Clinical Answers logo ] One meta-analysis has shown that antivirals used prophylactically may reduce the spread of symptomatic influenza within households.[121]

Antibiotic therapy

Antibiotic therapy may be required for certain complications of acute influenza, such as bacterial pneumonia, sinusitis, or otitis media.

Secondary bacterial pneumonia is an important complication of seasonal influenza and contributes to 25% of all seasonal influenza deaths.[93] The most common bacteria associated with pneumonia in the context of influenza co-infection are Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. Antibiotics should target these organisms.[2]

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