What is the recommended treatment for patients with influenza?

Treatment of Influenza

Start antiviral treatment immediately with a neuraminidase inhibitor (oseltamivir 75 mg orally twice daily for 5 days) for all hospitalized patients, those with severe/progressive illness, high-risk patients (including those with chronic conditions, immunocompromised, age <2 years or ≥65 years, pregnant/postpartum women), regardless of symptom duration. 1

Antiviral Treatment: Patient Selection

Mandatory Treatment Groups (Start Immediately)

• All hospitalized patients with influenza, regardless of illness duration prior to hospitalization 1
• Outpatients with severe or progressive illness, regardless of illness duration 1
• High-risk outpatients, including those with chronic medical conditions (cardiac, pulmonary, renal, metabolic) and immunocompromised patients 1
• Children <2 years and adults ≥65 years 1
• Pregnant women and those within 2 weeks postpartum 1

Optional Treatment (Consider for Otherwise Healthy Outpatients)

• Antiviral treatment can be considered for adults and children who are not at high risk, particularly if presenting within 48 hours of symptom onset 1
• The 48-hour window is a guideline for optimal efficacy in uncomplicated cases, but do not withhold treatment from high-risk or severely ill patients beyond this window 1, 2

Antiviral Agent Selection and Dosing

First-Line Monotherapy Options

Use a single neuraminidase inhibitor—do not combine NAIs 1:

• Oseltamivir (preferred oral agent): 75 mg orally twice daily for 5 days 1, 2

  • Reduce dose to 75 mg once daily if creatinine clearance <30 mL/min 1, 2
  • Available as oral suspension (6 mg/mL) for patients unable to swallow capsules 2

• Zanamivir (inhaled): 10 mg (two inhalations) twice daily for 5 days 1

  • Caution: Risk of life-threatening bronchospasm; avoid in patients with underlying respiratory disease 3

• Peramivir (intravenous): Single 600 mg IV dose 1

• Baloxavir marboxil: Single weight-based oral dose (40 mg for 20-<80 kg; 80 mg for ≥80 kg) 4, 5

  • Conditionally recommended by WHO for non-severe influenza in high-risk patients 5
  • Avoid coadministration with dairy products, calcium-fortified beverages, or polyvalent cation-containing products (antacids, laxatives, supplements) 4

Duration Modifications

• Standard duration: 5 days for uncomplicated influenza 1, 2
• Extended duration: Consider longer treatment for immunocompromised patients or those with severe lower respiratory tract disease (pneumonia, ARDS), as viral replication is often protracted 1

Critical Dosing Pitfalls

• Do not routinely use higher doses of FDA-approved NAI drugs for seasonal influenza 1
• Patients unable to mount adequate febrile response (immunocompromised, very elderly) may still benefit from antivirals despite lack of documented fever 1

Management of Bacterial Coinfection

When to Investigate and Treat Bacterial Coinfection

Empirically treat bacterial coinfection in addition to antivirals for 1:

• Patients presenting initially with severe disease (extensive pneumonia, respiratory failure, hypotension, persistent fever)
• Patients who deteriorate after initial improvement, particularly those on antivirals

Consider investigating bacterial coinfection for 1:

• Patients who fail to improve after 3-5 days of antiviral treatment

Antibiotic Selection Strategy

For uncomplicated influenza without pneumonia 1, 6:

• Previously healthy adults with acute bronchitis complicating influenza do not routinely require antibiotics
• Consider antibiotics only if worsening symptoms develop (recrudescent fever, increasing dyspnea)

For influenza-related pneumonia (non-severe) 1, 6:

• First-line oral: Co-amoxiclav OR tetracycline
• Alternative oral: Macrolide (clarithromycin/erythromycin) OR respiratory fluoroquinolone (for penicillin intolerance or coverage of S. pneumoniae and S. aureus)

For severe influenza-related pneumonia 1:

• Parenteral therapy: IV co-amoxiclav OR second/third-generation cephalosporin (cefuroxime, cefotaxime) PLUS macrolide
• Target coverage for S. pneumoniae and S. aureus (more common during influenza outbreaks than routine community-acquired pneumonia) 6

Antibiotic Duration

• Non-severe pneumonia: 7 days 7
• Severe, microbiologically undefined pneumonia: 10 days 7
• Confirmed/suspected S. aureus or Gram-negative pneumonia: 14-21 days 7

Monitoring for Treatment Failure

Investigate Alternative Causes or Resistance If:

• Patient fails to improve or deteriorates despite antiviral treatment 1
• Evidence of persistent influenza viral replication after 7-10 days (persistently positive RT-PCR or viral culture) 1

Consider NAI Resistance Testing For:

• Patients developing laboratory-confirmed influenza while on or immediately after NAI chemoprophylaxis 1
• Immunocompromised patients with persistent viral replication (>7-10 days) who remain ill during/after NAI treatment 1
• Patients inadvertently receiving subtherapeutic NAI dosing 1
• Severe influenza patients not improving with NAI treatment and persistent viral replication 1

Therapies to AVOID

Do NOT use 1:

• Corticosteroid adjunctive therapy for seasonal influenza, influenza-associated pneumonia, respiratory failure, or ARDS (unless clinically indicated for other reasons such as COPD exacerbation or septic shock)
• Combination neuraminidase inhibitors
• Routine immunomodulation with intravenous immunoglobulin preparations

Prophylaxis Considerations

Post-exposure prophylaxis (initiate within 48 hours of contact with infected individual) 1, 2, 4:

• Oseltamivir: 75 mg orally once daily for at least 10 days
• Baloxavir: Single weight-based dose (same as treatment dosing) 4, 5
• Immunocompromised patients: May continue prophylaxis up to 12 weeks 2

Seasonal prophylaxis during community outbreak 1, 2:

• Oseltamivir: 75 mg orally once daily for up to 6 weeks
• Protection lasts only as long as dosing continues 2

Supportive Care

• Antipyretics for fever control (avoid aspirin in children due to Reye's syndrome risk) 7, 8
• Adequate hydration 7
• Nutritional support in severe or prolonged illness 1
• Oxygen therapy as needed to maintain saturation 1
• Non-invasive ventilation may be considered as bridge to invasive ventilation when ICU beds are limited (in experienced centers with appropriate infection control) 1

Common Pitfalls

• Do not delay antiviral treatment in high-risk or severely ill patients waiting for laboratory confirmation—treat on clinical suspicion 1
• Do not withhold antivirals from hospitalized or severely ill patients beyond 48 hours of symptom onset 1
• Watch for secondary bacterial pneumonia typically developing 4-5 days after initial influenza symptoms 6, 8
• Remember that most influenza-like illnesses are not influenza—consider alternative diagnoses if no improvement with appropriate treatment 1, 3
• Stay informed on current CDC and WHO surveillance data regarding NAI-resistant influenza viruses and adjust treatment accordingly 1