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Wise Use of Antibiotics: Flu Season Playbook: Antivirals, Prophylaxis and When to Reach for Antibiotics

As the weather gets colder and the days get shorter, it is time to start thinking about influenza. Activity usually increases in October or November, but surveillance suggests an earlier start this year, with West Coast cases reported in August and September.1

Influenza can cause substantial morbidity and mortality in children. The 2024–2025 season included 297 reported pediatric deaths, the most since reporting began in 2004.2 Complications can include anything from acute otitis media and bacterial pneumonia to myocarditis and influenza-associated encephalopathy.3 While antivirals may shorten symptoms and reduce complications, pediatric prescribing remains inconsistent. In a recent survey, pediatric clinicians recommended oseltamivir in only 36.2% of scenarios, although most met treatment criteria in guidelines. Key barriers were limited guideline awareness, uncertainty about effectiveness and concerns about adverse effects.4

Who should receive antiviral treatment?

The American Academy of Pediatrics (AAP) recommends treatment for children with suspected or confirmed influenza who are hospitalized or have severe, complicated or progressive illness. Outpatients should be treated if they are at high risk, which includes children aged <2 years and those with underlying conditions (see Table 2). Treatment should also be considered for children with high-risk household contacts or contacts £6 months old. While the greatest benefit occurs when antivirals are started within 48 hours of symptoms, treatment should be given regardless of illness duration for these groups. For otherwise healthy outpatients with mild to moderate illness, consider treatment if it can begin within 48 hours of symptom onset.2

Although evidence that antivirals prevent hospitalization has been debated, a recent retrospective case-control study of approximately 15,000 outpatient children in Taiwan found that early treatment was associated with about 80% lower odds of influenza-related hospitalization. Although derived from an observational study, these findings provide additional support for early treatment.4

Which antiviral should be used?  

Oseltamivir (Tamifluâ) is the preferred antiviral for most children and hospitalized patients because of extensive clinical experience, low cost and favorable safety profile. It is approved for treatment in children aged ³2 weeks and is administered twice daily for five days. Generic capsules and oral suspension are available, and if suspension cannot be obtained, capsules may be opened and mixed with a sweetened liquid (e.g., chocolate syrup).5 In addition to reducing hospitalizations, oseltamivir shortened illness by 17.6 hours and reduced risk of otitis media by 34%.6 Among hospitalized children, treatment was associated with a 31% lower hazard of intensive care unit admission.7

Although gastrointestinal effects are a common concern, vomiting occurred in only 5.8% of oseltamivir-treated patients in randomized trials. Giving oseltamivir with food and using antiemetics when appropriate may help with tolerability. Neuropsychiatric effects, including confusion, delirium and hallucinations, have also raised concerns. However, influenza itself can cause these symptoms, and a causal relationship with oseltamivir has not been established. In a population-based cohort of more than 150,000 children, serious neuropsychiatric events were rare (51 per 100,000 person-weeks overall) and occurred at similar rates in patients who did and did not receive oseltamivir.8

Approved in 2018, baloxavir marboxil (Xofluzaâ) is a single-dose oral antiviral for uncomplicated influenza in healthy patients aged ³5 years and all individuals aged ³12 years, including those at high risk.2,9 It is an alternative for patients who cannot tolerate oseltamivir, but is generally not recommended for hospitalized or severely immunocompromised patients because of limited clinical data.2 Compared with oseltamivir, baloxavir marboxil reduced duration of fever by approximately 13 hours and decreased viral shedding/transmission, although duration of illness and rates of adverse effects were similar.2,10 Common adverse effects in children include vomiting and diarrhea.9 Treatment-emergent antiviral resistance is more common with baloxavir marboxil than with oseltamivir, especially in patients under 5 years old.2

Although an oral suspension formulation of baloxavir marboxil is FDA approved, it has been unavailable in the United States for several seasons. Crushing tablets is not recommended because of limited data and potential changes to the pharmacokinetics of the medication.9 Historically, baloxavir marboxil has been substantially more expensive than oseltamivir (about $200 versus $20 per course).5,9 The first generic tablets were approved in June 2026, but availability and pricing remain uncertain.

What about prophylaxis?

For exposed patients, the AAP recommends considering antiviral prophylaxis for patients within 48 hours of exposure for children ³3 months old at high risk of influenza complications who are under vaccinated, unlikely to have mounted a vaccine immune response or inadequately protected by the vaccine strain. Prophylaxis may also be considered for close contacts of high-risk children when the contacts are under vaccinated or vaccination is unlikely to provide adequate protection. Oseltamivir is the preferred agent for prophylaxis and is given once daily for seven days. A single dose of baloxavir marboxil is an alternative for patients ³5 years old.2  

Remember vaccination!

Annual influenza vaccination is the primary strategy to reduce the risk of severe disease and complications in children. In the 2024-2025 season, 89% of vaccine-eligible children who died from influenza were not fully vaccinated.11 Influenza vaccine is recommended for everyone ³6 months old. Individuals who are <9 years at the time of first influenza vaccination who have not received at least two lifetime doses of influenza vaccine prior to the current season require two doses of influenza vaccine given four weeks apart.2 The AAP has a variety of resources to promote influenza vaccine uptake which can be accessed here.   

Lastly, don’t forget your antibiotic stewardship!

Influenza can predispose children to secondary bacterial infections, especially those caused by Streptococcus pneumoniae, Staphylococcus aureus and group A Streptococcus.2 Because viral and bacterial symptoms overlap, assess the likelihood of bacterial disease before prescribing antibiotics. For example, watchful waiting is appropriate for selected patients with suspected otitis media. See Children’s Mercy Antimicrobial Stewardship resources for tips on diagnosis, antibiotic selection/duration and family education.

In conclusion, timely antiviral treatment can improve outcomes in children with influenza. This season, revisit your influenza playbook: follow guideline-based antiviral recommendations, promote vaccination and practice antibiotic stewardship to ensure the best outcomes for children.

References:

  1. CBS Mornings. Flu season got an early start. Here’s what to know. YouTube. Published October 7, 2026. Accessed October 8, 2026. https://www.youtube.com/watch?v=f28pw9vYkLg
  2. American Academy of Pediatrics, Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2026-2027: technical report. Published online August 10, 2026. doi:10.1542/peds.2026-078778
  3. Fazal A, Harker EJ, Neelam V, et al; CDC Influenza-Associated Encephalopathy Collaborators. Pediatric influenza-associated encephalopathy and acute necrotizing encephalopathy – United States, 2024-2025 influenza season. MMWR Morb Mortal Wkly Rep. 2025;74(36):556-564.
  4. Huang YN, Chang CJ, Dia YL, et al. Early antiviral therapy in pediatric outpatients and risk of influenza-related hospitalization. Pediatrics. 2026;158(3):e2025075020. doi:10.1542/peds.2025-075020
  5. In: Lexi-Drugs. UpToDate Lexidrug. UpToDate Inc. Updated October 2, 2026. Accessed October 9, 2026. https://online.lexi.com
  6. Malosh RE, Martin ET, Heikkinen T, et al. Efficacy and safety of oseltamivir in children: systematic review and individual patient data meta-analysis of randomized controlled trials. Clin Infect Dis. 2018;66(10):1492-1500.
  7. Rytlewski K, Dunn A, O’Halloran A, et al. Effectiveness of oseltamivir in hospitalized children with laboratory-confirmed influenza, 2014-2023. JAMA Pediatr. 2026;180(10):1116-1124.
  8. Antoon JW, Williams DJ, Bruce J, et al. Population-based incidence of influenza-associated serious neuropsychiatric events in children and adolescents. JAMA Pediatr. 2023;177(9):967-969.
  9. Baloxavir marboxil. In: Lexi-Drugs. UpToDate Lexidrug. UpToDate Inc. Updated August 4, 2026. Accessed October 9, 2026. https://online.lexi.com
  10. Ji Y, Yang W, Wang W. Comprehensive evaluation of therapeutic effectiveness and safety profiles of baloxavir marboxil for managing influenza virus infection in pediatric populations: a systematic review with pooled meta-analytic data. Front Pediatr. 2026;13:1733111.
  11. Reinhart K, Huang S, Kniss K, Reed C, Budd A. Influenza-associated pediatric deaths – United States, 2024-2025 influenza season. MMWR Morb Mortal Wkly Rep. 2025;74(36):565-569.
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