What is the treatment for influenza and its potential complications?

Treatment of Influenza

Initiate antiviral treatment with oseltamivir (75 mg orally twice daily for 5 days) or zanamivir immediately for all hospitalized patients, those with severe/progressive illness, and high-risk outpatients with suspected influenza—ideally within 48 hours of symptom onset, though treatment should not be withheld in severely ill patients even beyond this window. 1, 2

Patient Selection for Antiviral Treatment

Mandatory Treatment Groups (Treat Immediately Without Waiting for Testing)

• All hospitalized patients with suspected or confirmed influenza, regardless of symptom duration 3, 1
• Patients with severe, complicated, or progressive illness of any duration 3, 2
• High-risk patients including:
  • Children <2 years (especially <6 months who have highest mortality) 3, 1
  • Adults ≥65 years 3, 1, 2
  • Pregnant women and postpartum women (within 2 weeks of delivery) 3, 1, 2
  • Immunocompromised patients 3, 1, 2
  • Patients with chronic conditions (pulmonary, cardiovascular, renal, hepatic, hematologic, metabolic, or neurologic disorders) 3, 1

Optional Treatment Groups

• Previously healthy outpatients with uncomplicated influenza may be considered for treatment if initiated within 48 hours of symptom onset, though benefit is modest 3, 1
• Children whose household contacts are <6 months or have high-risk conditions 3

Antiviral Medications and Dosing

First-Line Treatment

Oseltamivir is the preferred neuraminidase inhibitor 3, 1, 4:

• Adults and adolescents ≥13 years: 75 mg orally twice daily for 5 days 1, 4
• Children ≥2 weeks old: FDA-approved with weight-based dosing 3, 4
• Dose adjustment: Reduce by 50% if creatinine clearance <30 mL/min 3

Alternative Options

• Zanamivir: Inhaled formulation, alternative to oseltamivir 3, 1
• Baloxavir: Single-dose option for patients ≥5 years, taken within 48 hours of symptom onset 5
• Peramivir: Intravenous alternative 1, 2

Medications to AVOID

• Amantadine and rimantadine: Do NOT use due to high resistance rates among circulating influenza A viruses 2, 6

Critical Timing Considerations

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

• Greatest benefit: Treatment initiated within 12-24 hours of symptom onset 3, 6
• Standard recommendation: Within 48 hours for outpatients 3, 1
• Hospitalized/severely ill patients: Treat even if >48 hours since onset, as observational studies show benefit up to 96 hours and beyond 3, 2, 7
• Extended treatment: Consider >5 days for patients with prolonged illness; doubling oseltamivir dose (150 mg twice daily) has been advocated for severely ill patients, though evidence is limited 3

Diagnostic Testing Approach

• Do NOT delay treatment while awaiting test results in high-risk or severely ill patients 3, 1
• Preferred test: RT-PCR or molecular assays (most accurate) 3, 1
• Rapid antigen tests: Less sensitive but acceptable when molecular testing unavailable 3
• Clinical diagnosis: Sufficient to initiate treatment during influenza season in appropriate patients 3, 8

Complications of Influenza

Primary Viral Complications

• Viral pneumonia: Can progress to respiratory failure and ARDS, requiring ICU admission 3
• Myocarditis and pericarditis 3
• Encephalitis and neurologic complications 3
• Exacerbation of underlying chronic conditions (asthma, COPD, heart failure, diabetes) 3

Secondary Bacterial Complications

Secondary bacterial pneumonia is a critical complication requiring specific management 3:

• Common pathogens: Streptococcus pneumoniae, Staphylococcus aureus (including MRSA), Streptococcus pyogenes 3
• Clinical indicators: Initial severe disease, clinical deterioration after initial improvement, or failure to improve after 3-5 days of antiviral treatment 1, 2

Antibiotic Management for Bacterial Coinfection

Add empiric antibiotics to antiviral therapy when bacterial coinfection is suspected 3, 1, 2:

For non-severe pneumonia (oral regimens preferred) 3:

• First-line: Co-amoxiclav or doxycycline 3, 1
• Alternative: Macrolide (clarithromycin/erythromycin) or respiratory fluoroquinolone (levofloxacin, moxifloxacin) 3

For severe pneumonia (parenteral regimens required) 3:

• Preferred: IV co-amoxiclav or 2nd/3rd generation cephalosporin (cefuroxime/cefotaxime) PLUS macrolide (clarithromycin/erythromycin) 3
• Alternative: Respiratory fluoroquinolone plus broad-spectrum β-lactamase stable antibiotic 3
• Timing: Administer within 4 hours of admission 3
• Duration: Typically 7 days; switch to oral when afebrile for 24 hours and clinically improving 3

Pediatric-Specific Complications

• Otitis media: Risk reduced by 34% with oseltamivir treatment 3
• Febrile seizures 3
• Croup and bronchiolitis 3

Monitoring for Treatment Failure

Investigate alternative diagnoses or bacterial coinfection if 1, 2:

• No improvement after 3-5 days of antiviral therapy 1, 2
• Clinical deterioration despite treatment 1, 2
• Persistent or recrudescent fever 3, 1

Special Populations

Hospitalized Patients

• Initiate treatment immediately regardless of time since symptom onset 3, 2
• Careful attention required to ventilator management, fluid management, and prevention/treatment of secondary bacterial pneumonia 3
• Consider extended treatment beyond 5 days for prolonged illness 3

Immunocompromised Patients

• May benefit from treatment even without documented fever 3
• Higher risk of prolonged viral shedding and complications 3
• Consider extended treatment duration 3

Pregnant and Postpartum Women

• High-risk group requiring immediate treatment 3, 1, 2
• Oseltamivir is safe and recommended 3

Infants and Young Children

• Infants <6 months: Highest hospitalization and death rates; oseltamivir approved from 2 weeks of age 3, 4
• Children <2 years: High-risk group requiring treatment 3, 1
• Common side effect: Vomiting occurs in ~15% (vs 9% placebo) 3

Common Pitfalls to Avoid

• Do NOT withhold treatment in severely ill patients beyond 48 hours—observational data supports benefit even with delayed initiation 3, 2, 7
• Do NOT use corticosteroids as adjunctive therapy for seasonal influenza 2
• Do NOT substitute antivirals for vaccination—annual influenza vaccination remains the primary prevention strategy 4, 5
• Do NOT use amantadine/rimantadine due to widespread resistance 2, 6
• Do NOT delay antibiotics when bacterial coinfection is suspected—empiric coverage should be added promptly 3, 1
• Avoid coadministration of oseltamivir or baloxavir with dairy products, calcium-fortified beverages, or polyvalent cation-containing supplements (calcium, iron, magnesium, zinc) as they reduce absorption 5

Antiviral Resistance Considerations

• Oseltamivir resistance: Rare overall (<1%), though up to 25% of seasonal H1N1 in Europe showed resistance historically 3, 7
• Monitor local surveillance data for resistance patterns 3, 2
• Neuropsychiatric effects: No established link between oseltamivir and neurologic/psychiatric events despite initial concerns 3