Influenza Treatment: Antiviral Therapy and Supportive Care
Immediate Antiviral Treatment Indications
All hospitalized patients with suspected or confirmed influenza must receive immediate antiviral therapy with a neuraminidase inhibitor, without waiting for laboratory confirmation and ideally within 48 hours of symptom onset. 1, 2
High-Risk Patients Requiring Immediate Treatment (Regardless of Symptom Duration)
- Children younger than 2 years and adults ≥65 years 1, 2, 3
- Pregnant women and women within 2 weeks postpartum 1, 2, 3
- Any degree of immunosuppression (including hematopoietic stem cell transplant recipients, patients on immunomodulators or biologics) 1, 3
- Chronic medical conditions: cardiac, pulmonary (including asthma), renal, hepatic, metabolic (including diabetes), neurologic disorders, hemoglobinopathies 1, 2, 3
- Patients with severe, complicated, or progressive illness at any point in disease course 1, 2
Otherwise Healthy Outpatients
- May be offered antiviral treatment if presenting within 48 hours of symptom onset, though benefit is modest (reduces illness duration by approximately 1 day) 1, 3, 4
- Greatest benefit occurs when treatment starts within 24 hours of symptom onset 2, 5
First-Line Antiviral Medications
Oseltamivir (Preferred Agent)
Oseltamivir 75 mg orally twice daily for 5 days is the first-line neuraminidase inhibitor for adults and adolescents ≥13 years 1, 2, 6
Pediatric Dosing (2 weeks through 12 years)
| Weight | Treatment Dose | Duration |
|---|---|---|
| ≤15 kg | 30 mg twice daily | 5 days |
| 15.1–23 kg | 45 mg twice daily | 5 days |
| 23.1–40 kg | 60 mg twice daily | 5 days |
| >40 kg | 75 mg twice daily | 5 days |
| <1 year | 3 mg/kg twice daily | 5 days |
- May be taken with or without food, though tolerability improves with food 6
- Adjust dose in renal impairment: reduce to 75 mg once daily if creatinine clearance <30 mL/min 3
Alternative Neuraminidase Inhibitors
Zanamivir: 10 mg (two 5-mg inhalations) twice daily for 5 days 1, 3
Peramivir: single 600-mg IV infusion for adults unable to tolerate oral medications 3
Baloxavir marboxil: single oral dose (40 mg if <80 kg; 80 mg if ≥80 kg) for patients ≥12 years 3, 8
- Avoid coadministration with dairy products, calcium-fortified beverages, or polyvalent cation supplements (calcium, iron, magnesium, zinc) 8
Extended or High-Dose Therapy Considerations
- Immunocompromised patients or those with severe lower respiratory tract disease (pneumonia, ARDS): consider extending oseltamivir beyond 5 days 2, 3, 9
- Higher-than-FDA-approved doses are not routinely recommended 2
- Combination therapy with two neuraminidase inhibitors is not recommended 2
Post-Exposure Prophylaxis
Indications for Chemoprophylaxis
- High-risk individuals for whom influenza vaccine is contraindicated, unavailable, or expected to have low effectiveness 1
- High-risk individuals during the 2 weeks after vaccination (before optimal immunity) 1
- Unvaccinated household contacts of high-risk individuals or infants <24 months 1
- Severely immunocompromised patients after household exposure 1
Dosing for Prophylaxis
- Oseltamivir 75 mg once daily for adults/adolescents ≥13 years 1, 6
- Duration:
- Must initiate within 48 hours of exposure; do not start if >48 hours have elapsed 1
Pediatric Prophylaxis Dosing (1–12 years)
| Weight | Prophylaxis Dose |
|---|---|
| ≤15 kg | 30 mg once daily |
| 15.1–23 kg | 45 mg once daily |
| 23.1–40 kg | 60 mg once daily |
| >40 kg | 75 mg once daily |
- Prophylaxis not approved for infants <1 year 6
Critical Prophylaxis Pitfall
If a patient on chemoprophylaxis develops symptoms, immediately switch to full treatment dosing (twice daily) and test for influenza; preferably use an antiviral with a different resistance profile if not contraindicated 1
Management of Bacterial Superinfection
When to Add Empiric Antibiotics
Empiric antibacterial therapy must be added when any of the following occur:
- Severe initial presentation: extensive pneumonia, respiratory failure, hypotension, or persistent high fever 2, 3, 9
- Clinical deterioration after initial improvement while on antiviral therapy 2, 3, 9
- Failure to improve after 3–5 days of antiviral treatment 2, 3, 9
Empiric Antibiotic Regimens
First-line (oral, non-severe): Co-amoxiclav 625 mg three times daily for 7 days 3, 9
Penicillin-allergic: Doxycycline 200 mg loading dose, then 100 mg once daily 3
Severe pneumonia (parenteral): IV co-amoxiclav or cephalosporin plus macrolide (covers Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus) 3, 9
Alternative: Respiratory fluoroquinolone (levofloxacin or moxifloxacin) 3
Monitoring and Red-Flag Symptoms
Expected Clinical Response
- Patients should show improvement within 48 hours of starting antivirals 3, 9
- Fever should resolve within 4–5 days; persistent fever warrants reassessment 3
Red-Flag Signs Requiring Urgent Evaluation
- Temperature >37.8°C with worsening respiratory symptoms 3
- Respiratory rate >24 breaths/min 3
- New confusion or altered mental status 3
- Inability to maintain oral intake 3
- Systolic blood pressure <90 mmHg 3
- New focal chest findings on examination 3
- Oxygen saturation <95% on room air 1
Two or more red-flag signs mandate consideration of hospital admission. 3
Resistance Testing Indications
Perform neuraminidase-inhibitor resistance testing in:
- Patients who develop influenza while on or immediately after chemoprophylaxis 2, 9
- Immunocompromised patients with persistent viral replication (typically after 7–10 days) who remain ill during or after treatment 2, 9
- Patients with severe influenza who do not improve with therapy and have ongoing viral replication 2, 9
- Individuals who may have received subtherapeutic dosing 2
Contraindicated Interventions
- Do not administer systemic corticosteroids for influenza treatment unless clinically indicated for other reasons (e.g., COPD or asthma exacerbation); corticosteroids are associated with increased mortality and bacterial superinfection 3, 9, 7
- Do not use amantadine or rimantadine due to >99% resistance rates in circulating strains 1, 3
- Do not delay antiviral treatment while awaiting laboratory confirmation in high-risk or severely ill patients 2, 9
Diagnostic Testing Guidance
- RT-PCR or rapid molecular assays are preferred for hospitalized patients (sensitivity 86–100%) 1, 9
- Rapid antigen tests have poor sensitivity (10–70%); negative results should not exclude influenza or delay treatment in high-risk patients 1, 9
- Multiplex RT-PCR panels should be used in immunocompromised patients to detect coinfections 9
- Do not wait for test results to initiate treatment in hospitalized or high-risk patients 1, 2, 9
Institutional Outbreak Management
- Implement outbreak control measures when 2 healthcare-associated laboratory-confirmed influenza cases are identified within 72 hours in the same ward/unit 1
- Administer antiviral chemoprophylaxis to all residents/patients in the involved unit for ≥2 weeks or until ~1 week after outbreak ends 1
- Offer prophylaxis to unvaccinated healthcare personnel in the involved unit 1