How should influenza A be treated, including antiviral options, dosing, timing, and recommendations for high‑risk patients?

Treatment of Influenza A

Start antiviral treatment immediately with a neuraminidase inhibitor (oseltamivir 75 mg orally twice daily for 5 days) for any patient with suspected or confirmed influenza A who is hospitalized, has severe/progressive illness, or belongs to a high-risk group—do not wait for laboratory confirmation and do not delay treatment beyond 48 hours of symptom onset. 1

Who Must Receive Antiviral Treatment

Mandatory treatment groups (start immediately regardless of illness duration):

• All hospitalized patients with suspected or confirmed influenza 1
• Outpatients with severe or progressive illness of any duration 1
• High-risk patients including:
  • Children younger than 2 years and adults ≥65 years 1
  • Pregnant women and those within 2 weeks postpartum 1
  • Immunocompromised patients (any degree of immunosuppression) 1, 2
  • Patients with chronic medical conditions (cardiac, pulmonary, renal, metabolic, or other chronic diseases) 1, 2

Optional treatment (consider if presenting within 48 hours):

• Otherwise healthy outpatients not at high risk for complications 1, 3

First-Line Antiviral Medication

Oseltamivir (Tamiflu) is the antiviral drug of choice: 2, 4

• Adults and adolescents ≥13 years: 75 mg orally twice daily for 5 days 1, 4
• Children 1-12 years: Weight-based dosing twice daily for 5 days 4
• Infants 2 weeks to <1 year: 3 mg/kg twice daily for 5 days 4

Alternative neuraminidase inhibitors: 1, 2

• Zanamivir (Relenza): 10 mg (two 5-mg inhalations) twice daily for 5 days 2
• Peramivir (Rapivab): Single 600-mg IV infusion for adults 2
• Baloxavir: Single 40-80 mg oral dose for patients ≥12 years 2

Do NOT use:

• Amantadine or rimantadine (>99% resistance rates among circulating strains) 2, 5
• Combination neuraminidase inhibitors 1
• Higher than FDA-approved doses routinely 1

Critical Timing Considerations

Optimal timing: 1, 2, 6

• Greatest benefit when started within 24 hours of symptom onset 6
• Standard recommendation: initiate within 48 hours of symptom onset 1, 4

Beyond 48 hours: 2, 5, 7

• Still treat hospitalized patients, severely ill patients, and high-risk patients even if >48 hours since symptom onset 2, 5, 7
• Observational studies suggest therapeutic benefit beyond 48 hours in these populations 7

Special Populations and Extended Treatment

Immunocompromised patients and severe disease: 1

• Consider longer duration of treatment beyond 5 days for documented or suspected immunocompromising conditions 1
• Consider extended treatment for severe lower respiratory tract disease (pneumonia or ARDS) as viral replication is often protracted 1

Renal impairment dosing adjustments: 4

• CrCl >30-60 mL/min: Reduce to 30 mg twice daily for 5 days 4
• CrCl >10-30 mL/min: Reduce to 30 mg once daily for 5 days 4
• ESRD on hemodialysis: 30 mg immediately, then 30 mg after every hemodialysis cycle (not to exceed 5 days) 4

Managing Bacterial Coinfection

Empirically add antibiotics in addition to antivirals when: 1, 2, 3

• Patients present initially with severe disease (extensive pneumonia, respiratory failure, hypotension, persistent fever) 1
• Clinical deterioration after initial improvement, particularly in those already on antivirals 1, 2
• Failure to improve after 3-5 days of antiviral treatment 1, 2

Preferred antibiotic regimens: 2

• Co-amoxiclav 625 mg orally three times daily for 7 days 2
• Doxycycline 200 mg loading dose, then 100 mg once daily (penicillin-allergic) 2, 3
• Coverage should include Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and especially Staphylococcus aureus 2

Monitoring for Treatment Failure

Reassess within 48-72 hours if: 2, 3

• No clinical improvement within 48 hours of starting antivirals 2
• Fever persists beyond 4-5 days without improvement 2
• New or worsening dyspnea, focal chest signs, tachypnea, or oxygen saturation <95% on room air 2

Investigate other causes besides influenza if patient fails to improve or deteriorates despite antiviral treatment 1, 5, 3

Resistance Testing Considerations

Consider neuraminidase inhibitor resistance testing for: 1

• Patients who develop laboratory-confirmed influenza while on or immediately after neuraminidase inhibitor chemoprophylaxis 1
• Immunocompromised patients with evidence of persistent viral replication (after 7-10 days) who remain ill during or after treatment 1
• Patients with severe influenza who do not improve with treatment and have persistent viral replication 1
• Patients who inadvertently received subtherapeutic dosing 1

Critical Pitfalls to Avoid

Do NOT: 2, 5, 7

• Use corticosteroids as adjunctive therapy for influenza treatment (associated with increased mortality and bacterial superinfection) 2, 5, 7
• Delay treatment waiting for laboratory confirmation in high-risk or severely ill patients 1, 2, 5
• Withhold treatment in hospitalized or high-risk patients presenting >48 hours after symptom onset 2, 5, 7
• Administer live attenuated influenza vaccine within 2 weeks before or 48 hours after oseltamivir use 4