Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

exposure to influenza in at-risk populations

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prophylactic antiviral therapy

Consider post-exposure antiviral chemoprophylaxis for: 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; 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.[2]​​[109][110]​​​ [ Cochrane Clinical Answers logo ]

One meta-analysis has shown that oseltamivir used prophylactically may reduce the spread of symptomatic influenza within households.[121] In phase 3 trials, single-dose baloxavir marboxil was effective in preventing influenza in household contacts (both adults and children) of patients with influenza.[133][134]

Oseltamivir can be used in adults and children of all ages, and is given for 10 days (up to 6 weeks during an epidemic) for this indication. It should be started within 2 days of exposure.

Zanamivir is given for 10 days in adults and children aged ≥5 years for this indication, and should be started within 2 days of exposure.

Baloxavir marboxil is given as a single dose to those aged 5 years or older (it is approved for patients 1 year and older in Europe). It should be given as soon as possible and within 2 days of exposure. Use of baloxavir is not recommended in people who are severely immunosuppressed.[110]

Pregnant women can be offered oseltamivir.[2][33]​​[110]

Primary options

oseltamivir: children <3 months of age: consult specialist for guidance on dose; children 3 months to <1 year of age: 3 mg/kg orally once daily; children ≥1 year of age and ≤15 kg body weight: 30 mg orally once daily; children ≥1 year of age and 15-23 kg body weight: 45 mg orally once daily; children ≥1 year of age and 23-40 kg body weight: 60 mg orally once daily; children ≥1 year of age and >40 kg body weight and adults: 75 mg orally once daily

OR

zanamivir inhaled: children ≥5 years of age and adults: 10 mg (two inhalations) once daily

OR

baloxavir marboxil: children ≥5 years of age (body weight <20 kg): 2 mg/kg orally as a single dose; children ≥5 years of age and adults (body weight 20-79 kg): 40 mg orally as a single dose; children ≥5 years of age and adults (body weight ≥80 kg): 80 mg orally as a single dose

ACUTE

adults

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antipyretic/analgesic

Antipyretics/analgesics are recommended for symptom relief of headache, fever, and myalgia.

Ibuprofen carries a greater risk of potentially serious adverse effects compared with paracetamol.

Primary options

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

OR

ibuprofen: 200-400 mg orally every 4-6 hours when required, maximum 2400 mg/day

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Consider – 

antiviral therapy

Treatment recommended for SOME patients in selected patient group

The US Centers for Disease Control and Prevention (CDC) recommends that 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]​​[110]​ While antivirals are approved by the US Food and Drug Administration (FDA) 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 benefits of treatment are greatest when medicines are initiated in the first 24-30 hours of symptom onset.[129]

Oseltamivir and zanamivir should be given within 2 days of onset of symptoms and given for 5 days for this indication. Peramivir is given as a single intravenous dose within 2 days of onset of symptoms.[2]​​[110]​ Peramivir may be recommended for those who are unable to take oral or inhaled neuraminidase inhibitors.

Inhaled and intravenous formulations of zanamivir are approved in Europe. Intravenous zanamivir is indicated for the treatment of complicated and potentially life-threatening influenza where other treatments for influenza, including the inhaled formulation of zanamivir, are unsuitable, and/or the patient's influenza virus is known or suspected to be resistant to other treatments. The recommended treatment course of intravenous zanamivir is 5-10 days.

Baloxavir marboxil, a polymerase acidic endonuclease inhibitor, is active against both influenza A and B and is given as a single oral dose. The FDA has approved baloxavir marboxil for the treatment of acute uncomplicated influenza in patients aged ≥5 years who have been symptomatic for no more than 48 hours, and who are otherwise healthy or at high risk of developing influenza-related complications. Use of baloxavir is not recommended in people who are severely immunosuppressed.[110]

Antivirals are not a substitute for the seasonal influenza virus vaccine.

Pregnant women presenting with uncomplicated illness due to influenza, and who have no evidence of systemic disease, can be offered oseltamivir.[2][33]​​[110]​​ 

Primary options

oseltamivir: 75 mg orally twice daily

OR

zanamivir inhaled: 10 mg (two inhalations) twice daily

OR

peramivir: 600 mg intravenously as a single dose

OR

baloxavir marboxil: body weight 20-79 kg: 40 mg orally as a single dose; body weight ≥80 kg: 80 mg orally as a single dose

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Plus – 

antibiotic therapy

Treatment recommended for ALL patients in selected patient group

Antibiotics should be reserved for certain complications of acute influenza, such as bacterial pneumonia or sinusitis.

The choice of antibiotics should be guided by Gram stain and culture, or provide empirical antibiotics effective against the most common bacterial pathogens following influenza, namely Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae (some examples of suitable empirical options are listed above).[2] Treatment can be instituted as an outpatient if the patient is not in respiratory distress and is haemodynamically stable. However, close monitoring and follow-up is required to assess if the patient needs admission for inpatient care.

When using fluoroquinolones, clinicians should be aware that they have been associated with disabling and potentially irreversible musculoskeletal and nervous system adverse events.[135][136] In addition, the US Food and Drug Administration (FDA) has issued warnings about the increased risk of aortic dissection, significant hypoglycaemia, and mental health adverse effects in patients taking fluoroquinolones.[137][138]

Fluoroquinolones are not recommended in pregnancy. However, cephalosporins are suitable for use in pregnant women.

Treatment course is generally 7-14 days.

Primary options

ceftriaxone: 2 g intravenously once daily

OR

cefotaxime: 1-2 g intravenously every 6-8 hours

OR

cefuroxime: 750-1500 mg intravenously every 6-8 hours

Secondary options

levofloxacin: 500 mg orally/intravenously once daily for 7-14 days; or 750 mg orally/intravenously once daily for 5 days

OR

moxifloxacin: 400 mg orally/intravenously once daily

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Plus – 

antibiotic therapy

Treatment recommended for ALL patients in selected patient group

Anti-staphylococcal coverage should be added when Staphylococcus aureus is a suspected source of infection. Suspicion for S aureus infection should be considered in patients with influenza and superimposed pneumonia on chest x-ray.

If S aureus infection is confirmed, broad-spectrum antibiotic therapy should be stopped and treatment continued with either oxacillin or nafcillin.

If MRSA is confirmed, broad-spectrum antibiotic therapy should be stopped and treatment continued with either vancomycin or linezolid.

Treatment course is generally 10-14 days; longer courses (up to 21 days) may be required for MRSA infection.

Primary options

oxacillin: 2 g intravenously every 4 hours

OR

nafcillin: 2 g intravenously every 4 hours

OR

vancomycin: 1 g intravenously every 12 hours

OR

linezolid: 600 mg intravenously/orally every 12 hours

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Consider – 

antibiotic therapy

Treatment recommended for SOME patients in selected patient group

Antibiotic therapy may be considered for patients with otitis media. Initial antibiotic treatment is with amoxicillin. Lack of improvement by 48-72 hours suggests that the initial therapy was not adequate. This is usually related to infection with an organism resistant to beta-lactam antibiotics (Haemophilus influenzae and drug-resistant Streptococcus pneumoniae), thus indicating the need for a beta-lactam-sensitive drug such as amoxicillin/clavulanate or a cephalosporin.

Either azithromycin or clarithromycin may be used as an alternative in penicllin-allergic patients. However, resistant pneumococcal isolates may not respond to this therapy.[139]

Amoxicillin and cephalosporins are considered safe in pregnant women.

Primary options

amoxicillin: 500-875 mg orally every 12 hours for 7 days

OR

amoxicillin/clavulanate: 500-875 mg orally every 12 hours for 7 days

More

Secondary options

cefdinir: 300 mg orally every 12 hours for 10 days

OR

cefuroxime: 250-500 mg orally every 12 hours for 10 days

Tertiary options

azithromycin: 500 mg orally once daily for 3 days

OR

clarithromycin: 250-500 mg orally every 12 hours for 7 days

children

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1st line – 

antipyretic/analgesic

Antipyretics/analgesics are recommended for symptom relief of headache, fever, and myalgia.

Ibuprofen carries a greater risk of potentially serious adverse effects compared with paracetamol.

Aspirin should not be administered to children aged <16 years due to the risk of Reye syndrome.

Primary options

paracetamol: 10-15 mg/kg orally every 4-6 hours when required, maximum 75 mg/kg/day

OR

ibuprofen: 5-10 mg/kg orally every 6-8 hours when required, maximum 30 mg/kg/day

Back
Consider – 

antiviral therapy

Treatment recommended for SOME patients in selected patient group

The US Centers for Disease Control and Prevention (CDC) recommends antiviral treatment is given as soon as possible for children with confirmed or suspected influenza who have severe, complicated, or progressive illness, or who require hospitalisation, as well as for children who are at higher risk for complications.[2]​​[110] While antivirals are approved by the US Food and Drug Administration (FDA) 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 benefits of treatment are greatest when medicines are initiated in the first 24-30 hours after symptom onset.[129][130]

Oseltamivir and zanamivir should be given within 2 days of onset of symptoms and given for 5 days for this indication. Peramivir may be given to children aged ≥6 months who have been symptomatic for no more than 2 days.[17]​​[110] Peramivir may be recommended for those who are unable to take oral or inhaled neuraminidase inhibitors.

Inhaled and intravenous formulations of zanamivir are approved in Europe. Intravenous zanamivir is indicated for the treatment of complicated and potentially life-threatening influenza in children aged ≥6 months where other treatments for influenza, including the inhaled formulation of zanamivir, are unsuitable, and/or the patient's influenza virus is known or suspected to be resistant to other treatments. The recommended treatment course of intravenous zanamivir is 5-10 days.

Baloxavir marboxil, a polymerase acidic endonuclease inhibitor, is active against both influenza A and B and is given as a single oral dose. The FDA has approved baloxavir marboxil for the treatment of acute uncomplicated influenza in children aged ≥5 years who have been symptomatic for no more than 48 hours, and who are otherwise healthy or at high risk of developing influenza-related complications. Use of baloxavir is not recommended in people who are severely immunosuppressed.[110]​ In Europe, baloxavir marboxil is approved for patients 1 year of age and older.

Antivirals are not a substitute for the seasonal influenza virus vaccine.

Children aged <1 year who have symptoms of seasonal influenza should be treated with oseltamivir.[110]​​

Primary options

oseltamivir: children <14 days of age: consult specialist for guidance on dose; children 14 days to 1 year of age: 3 mg/kg orally twice daily; children ≥1 year of age and ≤15 kg body weight: 30 mg orally twice daily; children ≥1 year of age and >15-23 kg body weight: 45 mg orally twice daily; children ≥1 year of age and >23-40 kg body weight: 60 mg orally twice daily; children ≥1 year of age and >40 kg body weight and children ≥13 years of age: 75 mg orally twice daily

OR

zanamivir inhaled: (inhaled) children ≥7 years of age: 10 mg (two inhalations) twice daily

OR

peramivir: children 6 months to 12 years of age: 12 mg/kg intravenously as a single dose, maximum 600 mg/dose; children ≥13 years of age: 600 mg intravenously as a single dose

OR

baloxavir marboxil: children ≥5 years of age (body weight <20 kg): 2 mg/kg orally as a single dose; children ≥5 years of age (body weight 20-79 kg): 40 mg orally as a single dose; children ≥5 years of age (body weight ≥80 kg): 80 mg orally as a single dose

Back
Plus – 

antibiotic therapy

Treatment recommended for ALL patients in selected patient group

Antibiotics should be reserved for certain complications of acute influenza, such as bacterial pneumonia or sinusitis.

The choice of antibiotics should be guided by Gram stain and culture, or provide empirical antibiotics effective against the most common bacterial pathogens following influenza, namely Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae (an example of suitable empirical option is listed above).[2] Treatment can be instituted as an outpatient if the patient is not in respiratory distress and is haemodynamically stable. However, close monitoring and follow-up is required to assess if the patient needs admission for inpatient care.

Treatment course is generally 7-14 days.

Primary options

ceftriaxone: 50-75 mg/kg/day intravenously

Back
Plus – 

antibiotic therapy

Treatment recommended for ALL patients in selected patient group

Anti-staphylococcal coverage should be added when Staphylococcus aureus is a suspected source of infection. S aureus infection should be suspected in patients with influenza and superimposed pneumonia on CXR.

If S aureus infection is confirmed, broad-spectrum antibiotic therapy should be stopped and treatment continued with either oxacillin or nafcillin.

If MRSA is confirmed, broad-spectrum antibiotic therapy should be stopped and treatment continued with either vancomycin or linezolid.

Treatment course is generally 10-14 days; longer courses (up to 21 days) may be required for MRSA infection.

Primary options

oxacillin: 100-200 mg/kg/day intravenously given in divided doses every 6 hours, maximum 12 g/day

OR

nafcillin: 50-200 mg/kg/day intravenously given in divided doses every 4-6 hours, maximum 12 g/day

OR

vancomycin: 10-15 mg/kg intravenously every 6 hours, maximum 2000 mg/day

OR

linezolid: 10 mg/kg intravenously/orally every 8 hours, maximum 600 mg/dose

Back
Consider – 

antibiotic therapy

Treatment recommended for SOME patients in selected patient group

Antibiotic therapy may be considered for patients with otitis media.[140]​​​ See Acute otitis media.

Initial antibiotic treatment is with amoxicillin.

Lack of improvement by 48-72 hours in a patient treated with antimicrobial therapy suggests that the initial therapy was not adequate. This is usually related to infection with an organism resistant to beta-lactam antibiotics (Haemophilus influenzae and drug-resistant Streptococcus pneumoniae), thus indicating the need for a beta-lactam-sensitive drug such as amoxicillin/clavulanate or a cephalosporin.

Either azithromycin or clarithromycin may be used as an alternative in penicillin-allergic patients. However, resistant pneumococcal isolates may not respond to this therapy.[139]

Primary options

amoxicillin: 80-90 mg/kg/day orally given in divided doses every 12 hours for 10 days

OR

amoxicillin/clavulanate: >3 months of age: 80-90 mg/kg/day orally given in divided doses every 12 hours for 10 days

More

Secondary options

cefdinir: >6 months of age: 14 mg/kg/day orally for 10 days

OR

cefuroxime: 30 mg/kg/day orally given in divided doses every 12 hours for 10 days

Tertiary options

azithromycin: >6 months of age: 10 mg/kg/day orally on the first day, followed by 5 mg/kg/day for 4 days; or 10 mg/kg/day orally for 3 days; or 30 mg/kg/day orally as a single dose

OR

clarithromycin: >6 months of age: 15 mg/kg/day orally given in divided doses every 12 hours for 10 days

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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