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
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 body weight ≤15 kg: 30 mg orally once daily; 15-23 kg: 45 mg orally once daily; 23-40 kg: 60 mg orally once daily; >40 kg and adults: 75 mg orally once daily
OR
zanamivir: children ≥5 years of age and adults: 10 mg (two inhalations) once daily
Consider post-exposure antiviral chemoprophylaxis 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;
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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.
One meta-analysis has shown that antivirals used prophylactically may reduce the spread of symptomatic influenza within households.[121]
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 1.5 to 2.0 days of exposure.
In view of the lower systemic exposure, zanamivir is recommended as first choice in pregnant women, although either drug can be used. In women who are breastfeeding, oseltamivir is preferred over zanamivir.
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
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.
complicated disease or at high risk of complications: presenting ≤48 hours after first symptoms
Treatment recommended for SOME patients in selected patient group
Primary options
oseltamivir: 75 mg orally twice daily
OR
zanamivir: 10 mg (two inhalations) twice daily
OR
peramivir: 600 mg intravenously as a single dose
OR
baloxavir marboxil: body weight 40-79 kg: 40 mg orally as a single dose; body weight ≥80 kg: 80 mg orally as a single dose
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.[109][2][112] 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.[128]
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.[109][112]Peramivir may be recommended for those who are unable to take oral or inhaled neuraminidase inhibitors.
Baloxavir marboxil, a polymerase acidic endonuclease inhibitor, is active against both influenza A and B. The FDA has approved baloxavir marboxil for the treatment of acute uncomplicated influenza in patients aged ≥12 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.
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 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.
with bacterial superinfection of unknown source: excluding otitis media
Treatment recommended for ALL patients in selected patient group
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
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 empiric 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.[130][131] In addition, the US Food and Drug Adminstration has issued warnings about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[132][133]
Fluoroquinolones are not recommended in pregnancy. However, cephalosporins are suitable for use in pregnant women.
Treatment course is generally 7-14 days.
suspected or known Staphylococcus aureus superinfection: excluding otitis media
Treatment recommended for ALL patients in selected patient group
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
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.
with otitis media
Treatment recommended for ALL patients in selected patient group
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
MoreSecondary 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
Otitis media may initially be treated 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.[134]
Amoxicillin and cephalosporins are considered safe in pregnant women.
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 4-6 hours when required, maximum 30 mg/kg/day
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.
complicated disease or at high risk of complications: presenting ≤48 hours after first symptoms
Treatment recommended for SOME patients in selected patient group
Primary options
oseltamivir: premature infants: consult specialist for guidance on dose; children <1 year of age: 3 mg/kg orally twice daily; children ≥1 year of age and body weight ≤15 kg: 30 mg orally twice daily; 15-23 kg: 45 mg orally twice daily; 23-40 kg: 60 mg orally twice daily; >40 kg: 75 mg orally twice daily
OR
zanamivir: children ≥7 years of age: 10 mg (two inhalations) twice daily
OR
peramivir: children ≥2 years of age: 12 mg/kg intravenously as a single dose, maximum 600 mg/dose
OR
baloxavir marboxil: children ≥12 years of age and body weight 40-79 kg: 40 mg orally as a single dose; children ≥12 years of age and body weight ≥80 kg: 80 mg orally as a single dose
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][109][112] 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.[135][128][136][129]
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 2 years and older who have been symptomatic for no more than 2 days.[109][112] Peramivir may be recommended for those who are unable to take oral or inhaled neuraminidase inhibitors.
Baloxavir marboxil, a polymerase acidic endonuclease inhibitor, is active against both influenza A and B. The FDA has approved baloxavir marboxil for the treatment of acute uncomplicated influenza in children aged ≥12 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.
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.[109]
with bacterial superinfection of unknown source: excluding otitis media
Treatment recommended for ALL patients in selected patient group
Primary options
ceftriaxone: 50-75 mg/kg/day intravenously
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 empiric 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.
suspected or known Staphylococcus aureus superinfection: excluding otitis media
Treatment recommended for ALL patients in selected patient group
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
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.
with otitis media
Treatment recommended for ALL patients in selected patient group
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
MoreSecondary 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
More than 80% of children with pneumococcal acute otitis media will respond to high-dose amoxicillin treatment.[137]
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.[134]
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