What is the recommended management for H3N2 (influenza A) positive cases?

Management of H3N2 Influenza A Positive Cases

Initiate oseltamivir 75 mg orally twice daily for 5 days as soon as possible after diagnosis, ideally within 48 hours of symptom onset, for all patients with confirmed or suspected H3N2 influenza. 1, 2

First-Line Treatment: Neuraminidase Inhibitors

Oseltamivir (Preferred Agent)

• Oseltamivir is the primary recommended antiviral for H3N2 treatment because H3N2 strains are resistant to adamantanes (amantadine/rimantadine) but remain susceptible to neuraminidase inhibitors 1
• Adult dosing: 75 mg orally twice daily for 5 days 1, 2
• Pediatric dosing (≥13 years): 75 mg orally twice daily for 5 days 1
• Pediatric dosing (<13 years): Weight-based dosing varies by age and weight 1
• Infants <1 year: Age-specific dosing ranges from 12 mg twice daily (≤3 months) to 25 mg twice daily (6-11 months) 1
• Take with food to enhance tolerability and reduce gastrointestinal side effects 2, 3

Zanamivir (Alternative Agent)

• Zanamivir 10 mg (2 inhalations) twice daily for 5 days is an equally acceptable alternative for patients without chronic respiratory disease 1, 4
• Contraindicated in patients with asthma or COPD due to bronchospasm risk 1, 4
• Approved for treatment in patients ≥7 years of age 1
• Administered via proprietary "Diskhaler" device, not through nebulizers or ventilators 1

Critical Treatment Principles

Timing of Initiation

• Maximum benefit occurs when treatment starts within 48 hours of symptom onset 1, 2
• Earlier initiation (within 24 hours) provides even greater benefit, reducing illness duration by up to 40% 5
• For hospitalized patients, initiate treatment regardless of time since symptom onset (even >48 hours) 1

High-Risk Patients Requiring Treatment

Treat all patients in the following categories immediately upon diagnosis: 1

• Children <2 years and adults ≥65 years
• Pregnant women and postpartum women (within 2 weeks of delivery)
• Patients with chronic pulmonary disease (including asthma), cardiovascular disease (except hypertension alone), renal, hepatic, hematologic, or metabolic disorders
• Neurologic and neurodevelopmental conditions (cerebral palsy, epilepsy, stroke, intellectual disability, muscular dystrophy)
• Immunosuppressed patients (medication-induced or HIV)
• Morbidly obese patients (BMI ≥40)
• Residents of nursing homes and chronic care facilities
• American Indian/Alaska Native persons
• Children <19 years receiving long-term aspirin therapy

Hospitalized Patients

• All hospitalized patients with suspected or confirmed influenza should receive antiviral treatment immediately 1
• Consider longer treatment courses (>5 days) for patients who remain severely ill after 5 days 1
• Add antibacterial therapy directed at S. pneumoniae, S. pyogenes, and S. aureus (including MRSA) for patients with community-acquired pneumonia when influenza is suspected 1

Dosage Adjustments

Renal Impairment

• Adjust oseltamivir dosing in moderate to severe renal impairment 2
• Not recommended for end-stage renal disease patients not undergoing dialysis 2

Severe Illness with Organ Replacement

• For patients requiring organ replacement therapy (ECMO, CVVHD), consider intravenous oseltamivir 100 mg twice daily rather than oral or renoprotective dosing to ensure reliable drug concentrations 6

Alternative Agents (Second/Third-Line)

Peramivir

• Intravenous peramivir is approved for acute uncomplicated influenza in patients ≥2 years who have been symptomatic ≤2 days 4
• Useful for patients unable to absorb oral medications or tolerate inhaled zanamivir 4

Baloxavir Marboxil

• Oral baloxavir (cap-dependent endonuclease inhibitor) approved for uncomplicated influenza in patients ≥12 years symptomatic ≤48 hours 4
• Different mechanism of action than neuraminidase inhibitors 4

Agents NOT Recommended

Do NOT use adamantanes (amantadine or rimantadine) for H3N2 treatment due to widespread resistance among H3N2 strains 1

Prophylaxis Considerations

Post-Exposure Prophylaxis

• Oseltamivir 75 mg once daily for 10 days initiated within 48 hours of exposure 1
• Particularly important for high-risk individuals exposed to confirmed cases 1

Seasonal Prophylaxis

• Oseltamivir 75 mg once daily during community outbreak periods 2
• Not a substitute for annual influenza vaccination 2

Clinical Outcomes

Expected Benefits

• Reduces illness duration by 1-1.5 days (25-30% reduction) when started within 36 hours 3, 5
• Reduces symptom severity by up to 38% 3
• Decreases secondary complications and antibiotic use 3
• 82% reduction in odds of in-patient death for hospitalized patients with H3N2 infection 7

Monitoring

• Consult CDC surveillance data routinely for current resistance patterns 1
• Monitor for treatment failure, which may indicate antiviral resistance 1

Common Pitfalls to Avoid

• Do not delay treatment waiting for laboratory confirmation in high-risk patients during influenza season 1
• Do not withhold treatment beyond 48 hours for hospitalized patients 1
• Do not use zanamivir in patients with underlying airway disease 1, 4
• Do not rely on rapid antigen tests alone as they have variable sensitivity; negative results do not rule out influenza 1
• Do not use oseltamivir as a substitute for vaccination 2