What is the recommended treatment for a patient presenting with influenza, particularly those with underlying health conditions or at high risk for complications?

Influenza Treatment

All patients with suspected or confirmed influenza who are hospitalized, severely ill, or at high risk for complications should receive immediate empiric treatment with oseltamivir 75 mg twice daily for 5 days, ideally within 48 hours of symptom onset, though treatment should not be withheld even if presenting beyond 48 hours. 1, 2

Who Requires Immediate Antiviral Treatment

High-risk patients requiring mandatory treatment include: 1, 2

• All hospitalized patients with suspected or confirmed influenza, regardless of symptom duration 1
• Children under 2 years of age (especially infants under 6 months) 1, 3
• Adults 65 years and older 1, 2
• Pregnant and postpartum women 1, 2
• Immunocompromised patients (including those on long-term corticosteroids, chemotherapy, transplant recipients) 1, 2, 3
• Patients with chronic medical conditions (cardiac disease, pulmonary disease including asthma/COPD, diabetes, renal disease, obesity) 1, 3
• Patients with severe, progressive, or complicated illness of any duration 1, 2

Previously healthy outpatients with uncomplicated influenza may be considered for treatment if initiated within 48 hours of symptom onset, though benefit is modest (approximately 1-1.5 day reduction in illness duration). 1, 4

Medication Selection and Dosing

First-Line Treatment: Oseltamivir

Standard dosing for adults and adolescents ≥13 years: 75 mg orally twice daily for 5 days 1, 3

Pediatric weight-based dosing (twice daily for 5 days): 1, 3

• ≤15 kg: 30 mg twice daily

• 15-23 kg: 45 mg twice daily

• 23-40 kg: 60 mg twice daily

• 40 kg: 75 mg twice daily

Renal dosing adjustment: Reduce dose by 50% if creatinine clearance <30 mL/min 1

Common adverse effects: Nausea (10% of patients) and vomiting (15% in children vs 9% placebo), which are transient and rarely lead to discontinuation. Taking with food reduces gastrointestinal symptoms. 5, 1, 3

Alternative: Zanamivir

Zanamivir 10 mg (two 5-mg inhalations) twice daily for 5 days is an alternative for patients who cannot tolerate oseltamivir or when oseltamivir resistance is suspected. 5, 6, 7

Important contraindication: Do not use zanamivir in patients with underlying airways disease (asthma, COPD) due to risk of serious, sometimes fatal bronchospasm. 6

Critical Timing Considerations

The 48-hour window is a guideline, not an absolute cutoff: 1, 2, 3

• Optimal benefit occurs when treatment starts within 48 hours of symptom onset, reducing illness duration by 1-1.5 days 1, 3, 4
• However, treatment initiated after 48 hours still provides substantial mortality benefit in high-risk and hospitalized patients (odds ratio for death = 0.21 when started up to 96 hours after onset) 5, 1, 3
• Never withhold treatment in hospitalized or high-risk patients based solely on time since symptom onset 5, 1, 2

Diagnostic Testing Approach

Do not delay treatment while awaiting laboratory confirmation in high-risk or severely ill patients. 1, 2, 3

Initiate empiric treatment based on: 1, 3

• Clinical presentation of influenza-like illness (acute onset fever with cough or sore throat)
• Local influenza activity in the community
• Patient risk factors

Testing considerations: 1

• RT-PCR or molecular assays are preferred diagnostic tests
• Rapid antigen tests have poor sensitivity; negative results should not exclude treatment in high-risk patients
• Testing is most useful when results will influence clinical management or infection control measures

Managing Bacterial Coinfection

Add empiric antibiotics to antiviral therapy when bacterial coinfection is suspected: 5, 1, 2

Clinical indicators suggesting bacterial superinfection: 1, 2

• Initial severe disease presentation
• Clinical deterioration after initial improvement
• Failure to improve after 3-5 days of antiviral treatment
• Recrudescent fever or increasing breathlessness
• New consolidation on chest imaging
• Purulent sputum production

Common bacterial pathogens: Streptococcus pneumoniae, Staphylococcus aureus (including MRSA), Streptococcus pyogenes, Haemophilus influenzae 5, 1

Antibiotic selection: 5, 1

• Non-severe pneumonia (outpatient): Doxycycline 200 mg loading dose then 100 mg daily OR co-amoxiclav 625 mg three times daily for 7 days
• Severe pneumonia (hospitalized): IV co-amoxiclav OR 2nd/3rd generation cephalosporin PLUS macrolide (clarithromycin preferred over azithromycin for better H. influenzae coverage)
• Previously well patients without pneumonia: Antibiotics not routinely required unless worsening symptoms develop 5

Special Populations and Extended Treatment

Immunocompromised patients: 1, 3

• May require treatment duration beyond 5 days due to prolonged viral shedding
• Should receive treatment regardless of fever documentation or time since symptom onset
• Clinical judgment should guide extension of therapy

Hospitalized patients with severe illness: 5, 1

• Treatment regimens may need extension beyond 5 days for prolonged illness
• Careful attention to ventilator management, fluid management, and prevention of secondary bacterial pneumonia is critical
• Double-dose oseltamivir (150 mg twice daily) has been studied but shows no significant survival benefit and is not recommended 8

Pregnant women: 1, 3

• Oseltamivir is safe and recommended during pregnancy
• Benefits outweigh risks; treatment should not be delayed

Prophylaxis Indications

Post-exposure prophylaxis with oseltamivir 75 mg once daily for 10 days should be considered for: 1, 3

• Household contacts of influenza-infected persons, especially high-risk individuals
• Residents of chronic care facilities during outbreaks (continue for ≥2 weeks or until 1 week after outbreak ends)
• Unvaccinated healthcare workers in outbreak settings caring for high-risk patients
• High-risk patients unable to be vaccinated

Prophylactic efficacy: 58.5-89% when started within 48 hours of exposure 3, 4

Important limitation: Prophylaxis initiated >48 hours after exposure is not recommended; instead, provide full-dose empiric treatment if symptoms develop. 3

Common Pitfalls to Avoid

Critical errors to avoid: 1, 2, 3

• Delaying or withholding oseltamivir while waiting for laboratory confirmation in high-risk patients—this is the most common and consequential error
• Refusing treatment to high-risk patients presenting >48 hours after symptom onset—multiple studies demonstrate mortality benefit up to 96 hours
• Using zanamivir in patients with underlying airways disease—risk of fatal bronchospasm 6
• Reflexively adding antibiotics for viral influenza symptoms alone—contributes to resistance; add only when bacterial coinfection is clinically suspected 5, 1
• Using amantadine or rimantadine—high resistance rates among circulating influenza A viruses make these ineffective 2
• Using corticosteroids as adjunctive therapy—not recommended for seasonal influenza treatment 2

Monitoring for Treatment Failure

Investigate alternative diagnoses or bacterial coinfection if: 1, 2

• No improvement after 3-5 days of antiviral therapy
• Clinical deterioration despite treatment
• Persistent or recrudescent fever
• Development of new respiratory symptoms or worsening breathlessness

Consider antiviral resistance if clinical deterioration occurs despite appropriate treatment, though resistance remains low (<5% in the United States for oseltamivir). 3