What are the latest recommendations for Respiratory Syncytial Virus (RSV) prophylaxis for high-risk infants, including those who are preterm or have underlying health conditions?

Latest RSV Prophylaxis Recommendations for Infants

All infants entering their first RSV season should receive nirsevimab (Beyfortus), a long-acting monoclonal antibody, as the primary prevention strategy, with palivizumab reserved only for specific high-risk populations who cannot receive nirsevimab. 1

Primary Prevention: Nirsevimab (Beyfortus) - First-Line for All Infants

Nirsevimab is now the standard of care for RSV prevention in infants, representing a major shift from the previous palivizumab-only approach. 2, 1

Dosing and Administration

• Single intramuscular dose based on weight at time of administration: 1

  • 50 mg if body weight <5 kg
  • 100 mg if body weight ≥5 kg
  • 200 mg for children entering their second RSV season (if indicated)

• Timing: Administer to all infants <8 months of age entering their first RSV season 2

• Duration of protection: A single dose provides protection for approximately 5 months, covering an entire RSV season 1

Efficacy Data

• 74.9% reduction in medically attended RSV lower respiratory tract infection in term and late preterm infants (≥35 weeks gestational age) 1

• 60.2% reduction in RSV hospitalizations in the same population 1

• Demonstrated safety and efficacy in preterm infants (<35 weeks GA) and those with chronic lung disease or hemodynamically significant congenital heart disease 1

Secondary Prevention: Palivizumab - For Specific High-Risk Populations

Palivizumab remains an option for high-risk infants who cannot receive nirsevimab or in specific clinical scenarios. 3

Eligibility Criteria for Palivizumab

• Infants born <29 weeks, 0 days' gestation who are <12 months old at the start of RSV season 4, 3

• Infants with chronic lung disease who required medical therapy within 6 months before RSV season start 3

• Children with hemodynamically significant congenital heart disease requiring medication for congestive heart failure 3, 5

• Children with pulmonary abnormalities or neuromuscular disease that impairs ability to clear upper airway secretions 3

• Immunocompromised children, including those with severe combined immunodeficiency (SCID) 2

Palivizumab Dosing Schedule

• 15 mg/kg intramuscularly once monthly throughout RSV season 3

• Maximum of 5 monthly doses per season 3

• Additional dose required after cardiac bypass surgery or ECMO due to 58% decrease in serum concentration 3

• First dose timing: 48-72 hours before hospital discharge or promptly after discharge for NICU infants 3

Critical Limitation of Palivizumab

Palivizumab has NO therapeutic benefit for treating established RSV infection—it is ONLY for prevention. If a child receiving palivizumab prophylaxis experiences breakthrough RSV hospitalization, discontinue further monthly doses as the likelihood of a second RSV hospitalization in the same season is extremely low. 2, 3

Universal Prevention Measures for ALL Infants

Beyond immunoprophylaxis, these non-pharmacologic interventions are essential for all infants: 4, 3

• Eliminate tobacco smoke exposure completely (including second-hand and third-hand exposure) 4

• Promote breastfeeding to decrease risk of lower respiratory tract disease 4, 3

• Limit exposure to crowds and group childcare settings during RSV season (November-March in most regions) 4, 3

• Emphasize hand hygiene in all settings, especially when contacts have respiratory infections 4

• Ensure influenza vaccination for infants ≥6 months and all household contacts 3

High-Risk Populations Requiring Lower Threshold for Hospitalization

Even with prophylaxis, certain infants warrant closer monitoring and earlier hospitalization: 6

• Infants <90 days of age (most hospitalizations occur during this period) 6

• Preterm infants <29 weeks GA (highest risk group) 6

• Infants with chronic lung disease requiring medical therapy 6

• Hemodynamically significant congenital heart disease 6

• Immunocompromised status (chemotherapy, transplant recipients, severe immunodeficiency) 6

• Neuromuscular disorders impairing secretion clearance 6

Common Pitfalls to Avoid

• Do NOT use palivizumab to treat active RSV infection—it has zero therapeutic benefit and is only for prevention 2, 3

• Do NOT withhold nirsevimab from otherwise healthy term infants—the new recommendation is universal prophylaxis for all infants entering their first RSV season 2, 1

• Do NOT forget the additional palivizumab dose after cardiac bypass surgery, as serum levels drop by 58% 3

• Do NOT continue palivizumab after breakthrough RSV hospitalization—discontinue further doses 3

• Do NOT rely solely on immunoprophylaxis—environmental measures (tobacco smoke elimination, hand hygiene, avoiding crowds) remain critical 4, 3

Key Differences from Previous Guidelines

The 2014 AAP guidelines restricted palivizumab to only the highest-risk infants (born <29 weeks GA), which led to increased RSV hospitalizations in the 29-34 week GA population. 7, 8 The introduction of nirsevimab represents a paradigm shift toward universal infant protection rather than targeting only the highest-risk groups. 2, 1