Author: Girotto, Jennifer

Oral Antibiotic Transition for Pediatric Endocarditis: Is it Ready for Prime Time?

By Hira Ilyas, PharmD

Dr. Pak and colleagues have recently published their early experience using intravenous to oral transition in pediatric endocarditis at Seattle Children’s hospital, which raises the question of whether this approach is ready for broader use.1,2 They reported on the use of intravenous to oral antibiotic transition in pediatric endocarditis from December 2022 to June 2024 (control: Dec 22-Nov 23; intravenous to oral protocol group Dec 23 – Jun 24). Patients were excluded from the study if they were diagnosed with fungal infective endocarditis or endovascular infection without vegetation.1,2

In the oral transitioned group (n=8), patients were 10 months to 20 years old and had antibiotics transitioned to oral as early as 7 days (n=4), 21 days (n=3), and 35 days (n=1), with an 88 percent success rate.1,2 Patients had primarily gram-positive pathogens, except for two cases: Serratia marcescens and Enterococcus faecalis (n=1) and Haemophilus parainfluenzae (n=1). Oral regimens included amoxicillin plus rifampin plus trimethoprim/sulfamethoxazole (n=1), amoxicillin (n=2), linezolid plus levofloxacin (n=2), levofloxacin (n=2), and trimethoprim/sulfamethoxazole plus ciprofloxacin (n=1).2 One patient failed to achieve clinical success, which was attributed to oncologic progression and death. In the control group (n=14), all patients were noted to have clinical success, but importantly 4 patients also received an oral transition despite the absence of a formal protocol at that time.1,2

What Can We Learn from Adult Intravenous to Oral Recommendations?

The Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial (also known as the POET trial) was published in 2019 looking to see if oral step-down therapy in patients with stable endocarditis would be safe and efficacious.3 This was a noninferiority, multicenter trial, with 400 adults who had stable left-sided endocarditis where 199 patients were randomized to continue intravenous treatment and 201 patients were switched to oral therapy.3 This trial targeted Streptococcus species, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci associated endocarditis. Additionally, the most common antibiotic regimens used included dicloxacillin and rifampicin (n=15) or amoxicillin and rifampicin (n=13) for S. aureus, amoxicillin and moxifloxacin (n=24) or amoxicillin and linezolid (n=13) for E. faecalis, amoxicillin and rifampicin (n=47) or amoxicillin and moxifloxacin (n=12) for Streptococcus species, and fusidic acid and linezolid (n=5) or rifampicin and linezolid (n=4) for coagulase-negative Staphylococcus species.3 Changing to the oral antibiotic treatment was noninferior to continued intravenous antibiotics treatment.3

There are multiple adult studies that further support intravenous to oral transition, primarily in patients with gram positive endocarditis.4-6 All but one required intravenous therapy for at least 10 days. The majority of the trials recommended dual oral therapy, although they noted some issues with this as well.

Guided by the POET trial, the ESC guidelines recommend switching patients to home oral antibiotic regimens for up to 6 weeks in the outpatient setting.7 To mimic the recommendation of the adult population, these guidelines suggest that before considering oral antibiotic therapy, stable patients are recommended to get a Transesophageal echocardiography.7  This differs from common pediatric practice, where transthoracic echocardiography is often preferred because it is noninvasive and performs well in children, particularly those weighing less than 60 kg, with reported sensitivity of 97% for detecting findings of infective endocarditis.8

A Promising Strategy, but Not Yet Routine Practice

Following the POET trial, intravenous-to-oral conversion for adult patients with left-sided endocarditis has increasingly become a standard of care. While oral step-down therapy for pediatric infective endocarditis remains preliminary, the early experience from Seattle Children’s hospital suggests this approach may be feasible in carefully selected patients. Pharmacists will be essential in evaluating oral bioavailability, organism-specific susceptibility, drug interactions, tolerability, adherence barriers, and monitoring needs as pediatric experience with this strategy evolves.

Oral Transition Therapies1,2,7

Condition or Organism Adult Oral Guideline Recommendations Pediatric Oral Antibiotic Transitions Used by Pak and Colleagues
Penicillin susceptible

Streptococcus species

amoxicillin + rifampin

amoxicillin + moxifloxacin

amoxicillin + linezolid

linezolid + rifampin

linezolid + moxifloxacin

amoxicillin
Penicillin resistant  Streptococcus species linezolid + rifampin

moxifloxacin + rifampin

linezolid + moxifloxacin

linezolid + levofloxacin
Penicillin and

Methicillin susceptible

S. aureus and coagulase-negative Staphylococcus species

amoxicillin + rifampin

amoxicillin + fusidic acid

moxifloxacin + rifampin

linezolid + rifampin

linezolid + fusidic acid

linezolid + levofloxacin

levofloxacin

Methicillin susceptible S. aureus and coagulase-negative Staphylococcus species dicloxacillin + rifampin

dicloxacillin + fusidic acid

moxifloxacin + rifampin

linezolid + rifampin

linezolid + fusidic acid

Methicillin resistant coagulase-negative Staphylococcus species linezolid + fusidic acid

linezolid + rifampin

linezolid
Enterococcus faecalis amoxicillin + moxifloxacin

amoxicillin + linezolid

amoxicillin + rifampin

linezolid + moxifloxacin

linezolid + rifampin

amoxicillin + rifampin +  sulfamethoxazole/trimethoprim
Coagulase-negative Staphylococcus species fusidic acid + linezolid

rifampicin + linezolid

amoxicillin + linezolid

*Positive blood cultures for Serratia marcescens and E. faecalis

Treatment duration of infective endocarditis varies by organism but is at least 4-6 weeks long. Enteral intervention in infective endocarditis patients can help reduce the risk associated with central line placement.

Hira Ilyas was a Doctor of Pharmacy candidate at the University of Connecticut. This post was written as part of her Advanced Pharmacy Practice Experience under the guidance of her professor, Jennifer Girotto PharmD, BCPPS, BCIDP, who also reviewed and edited the piece.

References:

  1. Pak D, McDonald DR, Brothers AW, et al. Switch to Oral Antibiotics for Infective Endocarditis in Children. Hosp Pediatr. 2025;16(1):e31–e35. doi:10.1542/hpeds.2025-008463
  2. Pak D, McDonald DR, Brothers AW, et al. Partial Oral Therapy for Pediatric Infective Endocarditis. 2025;14(Supplement_1):S12. https://10.1093/jpids/piaf072.021
  3. Iversen K, Ihlemann N, Gill SU, et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. New England Journal of Medicine. 2019;380(5):415–424. doi:10.1056/NEJMoa1808312
  4. Freling S, Wald-Dickler N, Banerjee J, et al. Real-World Application of Oral Therapy for Infective Endocarditis: A Multicenter, Retrospective, Cohort Study. Clin Infect Dis. 2023;77(5):672–679. doi:10.1093/cid/ciad119
  5. Pries-Heje MM, Hjulmand JG, Lenz IT, et al. Clinical implementation of partial oral treatment in infective endocarditis: the Danish POETry study. Eur Heart J. 2023;44(48):5095–5106. doi:10.1093/eurheartj/ehad715
  6. Rallet B, Pouy R, Coutureau C, et al. Should We Extend the Use of Oral Antibiotics in Infective Endocarditis? The ENDO-ORAL Study. Clin Infect Dis. 2026;82(3):e462–e470. doi:10.1093/cid/ciaf452
  7. Delgado V, Ajmone Marsan N, de Waha S, et al. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J. 2023;44(39):3948–4042. doi:10.1093/eurheartj/ehad193
  8. Aldrich JB, Madsen N, Armstrong AK, et al. Evaluation and treatment of infective endocarditis in children and adolescents with underlying CHD: a Paediatric Acute Care Cardiology Collaborative Clinical Practice Guideline. Cardiology in the Young. 2025;35(12):2422–2440. doi:10.1017/S1047951125110561

 

Watchful Waiting in Uncomplicated Acute Otitis Media: When Less Treatment Results in Improved Care

By Timothy Rodrigue, PharmD 

Antibiotics are commonly prescribed in children for the treatment of acute otitis media (AOM)1. AOM is very prevalent with approximately 23% and 60% of children diagnosed by ages 1 and 3 years, respectively.2 Despite the high prevalence of AOM in young children, uncomplicated AOM is generally a self-limiting disease. In the vast majority of children, the earache will resolve without treatment in seven to eight days.3 Watchful waiting is a choice to withhold antibiotics and observe the clinical presentation of the patient with a plan to initiate antibiotics only if there is worsening or no improvement of symptoms by 48 to 72 hours.1 This watchful waiting strategy is recommended for many children by the  American Academy of Pediatrics (AAP) AOM guidelines.1 Their rationale is that the use of watchful waiting will result in less antibiotic prescriptions, decrease the frequency of antibiotics prescribed and thus the development of complications from antibiotic usage including: promotion of antibiotic resistant strains, adverse effects, and increased healthcare costs.1 Data have also demonstrated low risk of complications including mastoiditis.

 A Practical Guide to AOM Management by Patient Type

The AAP AOM guidelines1 currently recommend watchful waiting in those with non-severe signs or symptoms (e.g., mild ear pain for less than 48 hours, temperature less than 102.2˚F, no otorrhea) with reliable follow-up in both:

  • young children 6 months to 23 months of age with unilateral AOM and
  • older children 24 months or older with unilateral or bilateral AOM.

It does not matter if watchful waiting is used or not, that all children are provided with systemic treatment (e.g., acetaminophen, ibuprofen) for pain and fever as antibiotic therapy does not relieve those symptoms within 24 hours.1,4

Evidence Supporting Watchful Waiting

I was surprised to see that in comparison to immediate antibiotics, watchful waiting (also referred to in clinical studies as delayed antibiotic therapy, observation period, or watchful waiting) has similar parent satisfaction with AOM care management.5 Immediate antibiotics have the benefit of fewer analgesic doses required (3.4 vs 7.7 doses, p<0.01) and quicker resolution.6 However this is only a modest overall clinical benefit in practice as antibiotics are not expected to work in the first 24 hours. In those treated with antibiotics, there are greater risks of: having antibiotic resistance to one or more medications (p<0.02) and penicillin resistant Streptococcus pneumoniae (p<0.04) and increased average antibiotic costs per patient ($47.41 vs $11.43).6  Additionally, a recent study also reported increased rates of antibiotic related adverse effects[RR 1.49, 95%CI (1.27-1.73)].7

Other studies have had similar cure rates noted in both watchful waiting and immediate therapy.8 A large retrospective observational study, published in July 2025, that included just over 140,000 pediatric visits for AOM had 15% use watchful waiting and both the watchful waiting and immediate treatment groups were found to have similar rates (1% in each group) of failure, evaluated between days 3 – 14.8  While a randomized clinical trial did demonstrate increased rates of clinical failure in those with watchful waiting.  Clinical failure, assessed at days 0-12, occurred in 21% of those in the watchful waiting group versus 5% given immediate antibiotics (p=0.001).6 Importantly, authors noted that AOM failure occurred much more frequently in both groups when they had recent antibiotic exposure, as defined as any antibiotic within the last 30 days.6   

Although, some parents and providers may still be hesitant to utilize watchful waiting because they are concern it will be associated with longer duration of symptoms and contribute to more work and school days missed. In one of the first studies evaluating this, authors reported a non-significant increased number of children and parents missed school or work in the delayed group [83% vs 69% for children; adjusted OR 1.66 (95% CI 0.58-4.72) and 71% vs 54% for parents; adjusted OR 1.66 (95% CI 0.67-4.11)].9 While a later study demonstrated a significant increase in school days missed [difference 1.45 days (95% CI 0.46 – 2.24)],10 this increase is likely minimal in real world practice and should not alone be a factor for avoiding watchful waiting.

Morin and colleagues recently estimated the impact that watchful waiting would have on percent of antibiotic exposure.  They suggest that if all adhered to the AAP recommendations and encouraged the use of watchful waiting when appropriate, the total days of antibiotic therapy would be reduced in ages 6 months through 17 years old by 19% (or 4.5 million days of therapy).11

Successful Strategies Implemented to Increase Usage of Watchful Waiting

Because watchful waiting is underutilized, there are several interventions that have demonstrated increased uptake of this process.  One approach is to provide a safety-net antibiotic prescription combined with parent education.  This approach recommends educating the parents on the signs and symptoms of AOM and sending a prescription to the pharmacy, with instructions on only filling after 2-3 days, if the child’s symptoms are not improving. To implement this technique, one hospital developed a treatment algorithm within the electronic health record interface and resources for prescribing.  Authors reported that this increased the likelihood of providers correctly identifying patients eligible for safety-net antibiotics from 26% at baseline to 50% after 20 months.12

Interventions help improve the delivery of information to caregivers. An example of this is the creation of the Ear Pain Decision Aid (earpaindecisionaid.org), an open-access tool that allows the parent to select the age of their child, which specific symptoms they are exhibiting, and explain the different options the parent has for treatment. Utilization of  the tool strengthened shared clinical decision making as parents being counseled with the aid scored greater in knowledge of treatment options compared to usual care (MD 1.0; 95% CI 0.3-3.7) with no significant difference in interaction time.13 Although the specific decision aid is no longer active online, other institutions can incorporate similar tools and use the Ear Pain Decision Aid as a model by visiting https://carethatfits.org/otitis-media/.

System level strategies including workstation notifications integrated with the electronic health record interface prompt providers to speak with the caregiver at the time a diagnosis for AOM is made.  Standardized templates and infographics explain the treatment algorithm and the benefits versus risks of certain treatment options. Quality improvement studies illustrate that applying these strategies increased adherence to guidelines from 78% to 98% and increased watchful waiting in safety net antibiotic eligible patients from 21% to 78%.14

Collectively, these interventions improve shared clinical decision-making by providing both providers and caregivers with accessible and standardized information. As a result, parents become more well-informed and confident about moving forward with the appropriate use of watchful waiting in non-severe AOM.

Pharmacists Role in AOM Stewardship

Watchful waiting is an effective management option for non-severe AOM and provides an opportunity to reduce unnecessary antibiotic exposure while maintaining high-quality patient outcomes. New evidence shows support for decreases in costs, antibiotic resistance, and adverse effects with watchful waiting. Pharmacists have a crucial role and opportunity for impact through antimicrobial stewardship. Looking forward, partnering pharmacists with pediatricians at the point of care would help to reinforce clinical decisions by aiding parent education with guideline directed data, open access decision aids, and addressing concerns thus instilling confidence in caregivers and reducing unnecessary antibiotic use.  In doing so, pharmacists can influence acceptance of watchful waiting and optimize patient care by reinforcing symptom identification and appropriate analgesia and help support shared-decision making.

Timothy Rodrigue was a Doctor of Pharmacy candidate at the University of Connecticut. This post was written as part of his Advanced Pharmacy Practice Experience under the guidance of her professor, Jennifer Girotto PharmD, BCPPS, BCIDP, who also reviewed and edited the piece.

References

  1. Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media. Pediatrics. 2013;131(3):964. doi:10.1542/peds.2012-3488
  2. Kaur R, Morris M, Pichichero ME. Epidemiology of Acute Otitis Media in the Postpneumococcal Conjugate Vaccine Era. Pediatrics. 2017;140(3):e20170181. doi: 10.1542/peds.2017–0181. Epub 2017 Aug 7. doi:10.1542/peds.2017-0181
  3. Thompson M, Vodicka TA, Blair PS, et al. Duration of symptoms of respiratory tract infections in children: systematic review. BMJ. 2013;347:f7027. doi:10.1136/bmj.f7027
  4. van Buchem FL, Dunk JH, van’t Hof MA. Therapy of acute otitis media: myringotomy, antibiotics, or neither? A double-blind study in children. Lancet. 1981;2(8252):883–887. doi:10.1016/s0140-6736(81)91388-x
  5. Chao JH, Kunkov S, Reyes LB, Lichten S, Crain EF. Comparison of two approaches to observation therapy for acute otitis media in the emergency department. Pediatrics. 2008;121(5):1352. doi:10.1542/peds.2007-2278
  6. McCormick DP, Chonmaitree T, Pittman C, et al. Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment. Pediatrics. 2005;115(6):1455–1465. doi:10.1542/peds.2004-1665
  7. Smolinski NE, Djabali EJ, Al-Bahou J, Pomputius A, Antonelli PJ, Winterstein AG. Antibiotic treatment to prevent pediatric acute otitis media infectious complications: A meta-analysis. PLoS One. 2024;19(6):e0304742. doi:10.1371/journal.pone.0304742
  8. Jenkins TC, Hersh AL, Stein AB, et al. Watchful Waiting for Children With Acute Otitis Media: Frequency of Use and Outcomes in Clinical Practice. J Pediatric Infect Dis Soc. 2025;14(12):piaf104. doi: 10.1093/jpids/piaf104.
  9. Burke P, Bain J, Robinson D, Dunleavey J. Acute red ear in children: controlled trial of non-antibiotic treatment in general practice. BMJ. 1991;303(6802):558–562. doi:10.1136/bmj.303.6802.558
  10. Tähtinen PA, Laine MK, Ruuskanen O, Ruohola A. Delayed versus immediate antimicrobial treatment for acute otitis media. Pediatr Infect Dis J. 2012;31(12):1227–1232. doi:10.1097/INF.0b013e318266af2c
  11. Morin TL, Stein AB, El Feghaly RE, et al. Interventions to Minimize Unnecessary Antibiotic Use for Acute Otitis Media: A Meta-Analysis. Children (Basel). 2025;12(10):1408. doi: 10.3390/children12101408. doi:10.3390/children12101408
  12. Daggett A, Wyly DR, Stewart T, et al. Improving Emergency Department Use of Safety-Net Antibiotic Prescriptions for Acute Otitis Media. Pediatr Emerg Care. 2022;38(3):e1151–e1158. doi:10.1097/PEC.0000000000002525
  13. Anderson JL, Oliveira J E Silva L, Hess EP, et al. Shared decision-making for pediatric acute otitis media in the United States: a randomized emergency department trial. BMC Emerg Med. 2025;25(1):146–w. doi:10.1186/s12873-025-01305-w
  14. Wolf RM, Langford KT, Patterson BL. Improving Adherence to AAP Acute Otitis Media Guidelines in an Academic Pediatrics Practice through a Quality Improvement Project. Pediatr Qual Saf. 2022;7(3):e553. doi:10.1097/pq9.0000000000000553

 

 

Resurgence of Lyme Disease: Key Insights for Pediatric Prophylaxis

Lyme Disease is being diagnosed earlier in the season and with increasing frequency. Diagnosed annual cases of Lyme Disease in the United States tripled from 2010 to 2023 (30,158 – 89,468).1 It is primarily concentrated in the Northeast and upper Midwest, with cases spanning from Maine through the Mid-Atlantic states and extending westward to Wisconsin.1 So far in 2026, data from both agricultural tick positivity and emergency department visits suggest further jumps.2,3 The highest number of ED visits reported were in children 0 to 9 years old, highlighting the importance of timely and appropriate prophylaxis a priority in children.2

Prophylaxis with Doxycycline Recommended for All Ages

Did you know that in 2018, the American Academy of Pediatrics changed their stance on the use of doxycycline for children less than 8 years old?  Specifically, they noted that doxycycline could be used in any age child for durations of up to 21 days?4  Further, the 2020 Lyme Disease Guidelines recommend the use of a single dose of doxycycline for prophylaxis (4.4 mg/kg up to max dose of 200 mg) for patients of any age (without contraindications) who meet prophylaxis criteria.5  Doxycycline is the only post-exposure prophylaxis that has shown to be effective in preventing Lyme Disease.5,6  When using single dose doxycycline, data suggest it is about 87% effective at preventing Lyme Disease.6

Lyme Disease Prophylaxis: for Who and with What?

The guidelines suggest using prophylaxis on the following patients: those who have had a deer tick (Ixodes scapularis) attached for at least 36 hours in an area where Lyme Disease is endemic. Further, the use of antibiotic prophylaxis must be given within 72 hours from the removal of the tick.5

There have been increases in the use of doxycycline as Lyme prophylaxis in young pediatric patients (i.e., < 8 years) since the change in recommendations, but it continues to be underutilized. Specifically, one study reported those 0 – 7 years had the lowest rates of doxycycline prophylaxis prescribed (0.76 per 10,000 in 0 -7 years versus 9.12 – 44.23 per 10,000 in adult age groups).7

Pharmacist Perspective

As pharmacists, we are often in a position to help identify appropriate patients, recommend doxycycline, and educate both caregivers and providers. Pharmacists who reside in states where Lyme Disease is endemic have the opportunity to make recommendations for optimal prophylaxis that will hopefully decrease incidence of Lyme Disease in children.

References:

  1. Centers for Disease Control and Prevention. Lyme Disease Case Maps. Accessed April 20, 2026. https://www.cdc.gov/lyme/data-research/facts-stats/lyme-disease-case-map.html
  2. Centers for Disease Control and Prevention. Tick Bite Data Tracker. Accessed April 20, 2026. https://www.cdc.gov/ticks/data-research/facts-stats/tick-bite-data-tracker.html
  3. The Connecticut Agricultural Experiment Station. CAES Alerts Residents of Increased Tick Activity and Emerging Disease Threats in Connecticut. Accessed April 20, 2026. https://portal.ct.gov/-/media/caes/press-room/caes-press-release-tick-activity-4-6-26.pdf
  4. Kimberlin DW, Jackson MA, Long SS. Lyme Disease. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2018 Report of the Committee on Infectious DiseasesAmerican Academy of Pediatrics; 2018
  5. Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology: 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease. Neurology. 2021;96(6):262–273.
  6. Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001;345(2):79–84.
  7. Marx GE, Beck A, Corey C, et al. Lyme Disease Prophylaxis by Single-Dose Doxycycline in the United States, 2010-2020. Open Forum Infect Dis. 2024;11(10):ofae593.

 

 

Congenital Syphilis Still an Issue, Pharmacotherapy Opportunities to Improve

Centers for Disease Control and Prevention (CDC) mentioned in September 2025, that congenital syphilis cases increased for the 12th consecutive year.1 This information, in combination with periodic shortages of Bicillin LA2, the primary treatment of syphilis in pregnancy, suggest it may not decrease soon.

Why is Congenital Syphilis an Issue?

Congenital syphilis is an issue because syphilis can be transmitted from the mother to the fetus.  It can result in still birth, preterm birth, low birthweight, and birth defects. Furthermore, in cases where the congenital syphilis goes untreated, the child can present with bone, teeth, eye and nervous system abnormalities, as well as hearing loss.3 Symptoms in infants include hematologic suppression (e.g., anemia, thrombocytopenia), liver and bone abnormalities, lesions, “snuffles”, seizures, as well as eye and nerve issues.3,4

Recent Data and Impact of Maternal Treatment and Timing on Infant Outcomes

Estimates suggest that about 16% of infants born to mothers with syphilis will have congenital syphilis.5 Carlson and colleagues reported the outcomes of 1682 infants born to mothers who were positive for syphilis from 2018-2021 in pregnancy. Their data reinforced that still birth is less common among those who received guideline recommended therapy (e.g., one-three doses of penicillin G started at least 30 days prior to delivery with appropriate spacing) versus no therapy (1.4% vs 10%; p<0.001).6 Among those with live births, receipt of guideline-recommended therapy showed differences versus both other treatment (either not penicillin based, not correct number, or did not start with at least 30 days before birth) for low birth weight (10% guideline, 25% other, 30% no treatment; p=0.02 vs no treatment; <0.001 vs inadequate treatment), and NICU stay overall (27% guideline, 57% other, 67% no treatment; p< 0.001 for both comparisons), including those ≥ 34 weeks gestation (25% guideline, 54% other, 63% no treatment; p< 0.001 for both comparisons).6 Further another meta-analysis also confirmed that guideline recommended therapy was associated with decreased risk of congenital syphilis versus penicillin therapy begun within 30 days of delivery.7 This meta-analysis included one study that used aminopenicillin (e.g., ampicillin, amoxicillin), and this group had a high rate of congenital syphilis.7 There was no control group, but until there is more data, these reinforce the recommendations for penicillin as the only recommended therapy for pregnancy treatment of syphilis. 4,8

Opportunity to Improve Congenital Syphilis Treatment

A recent study by Nlandu and colleagues published in March 2026 in the Pediatric Infectious Diseases Journal, suggests that many newborns are not receiving appropriate treatment.9 Specifically, even among those newborns meeting criteria for either proven or highly probably congenital syphilis, only about 67% received guideline recommended therapy with 10 days of penicillin G IV therapy.9 The others received either a single dose of benzathine penicillin G (14.5%), another non recommended treatment (3.9%), or no treatment at all (14.5%).9 As pharmacists, we are in a role to be able to help providers ensure that patients receive the optimal therapy to prevent and treat congenital syphilis.10

Recommended Treatment of Congenital Syphilis

Both the CDC and the American Academy of Pediatrics agree upon the general approach for the treatment of congenital syphilis.4,8 Essentially, aqueous penicillin G administered IV at a dose of 50,000 units/kg/dose every 12 hours, then changed on day 8 of life to every 8 hours to complete 10 days of therapy, is recommended. Alternative therapy with procaine penicillin G intramuscularly at 50,000 units/kg/day IM can be used either for 10 days (proven, highly probable, or possible syphilis), or as a single dose for those with possible syphilis if clinicians think it is less likely and have reason to believe in reliable follow-up. 4,8 Lastly, in cases when syphilis is less likely or unlikely, then either a single dose or close follow-up is recommended. 4,8

References:

  1. Centers for Disease Control and Prevention&nbsp. 2024 Annual Sexually Transmitted Infections Surveillance report. Accessed April 3, 2026. https://www.cdc.gov/sti-statistics/annual/index.html
  2. Centers for Disease Control and Prevention. CDC NCHHSTP: Bicillin L-A Shortage. Accessed April 3, 2026. https://www.cdc.gov/nchhstp/director-letters/bicillin-update.html
  3. Sandoval C. Syphilis Complicating Pregnancy and Congenital Syphilis. N Engl J Med. 2024;390(13):1251.
  4. Kimberlin DW, Banerjee R, Barnett ED, Lynfield R, Sawyer MH. Red Book: 2024-2027 Report of the Committee on Infectious Diseases. 33rd ed. American Academy of Pediatrics; 2024
  5. Gomez GB, Kamb ML, Newman LM, et al. Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis. Bull World Health Organ. 2013;91(3):217–226.
  6. Carlson JM, Sancken CL, Nguyen K, et al. Birth Outcomes Among Women With Syphilis During Pregnancy in Six U.S. States, 2018-2021. Obstet Gynecol. 2025;146(1):121–128.
  7. Gutiérrez-Tamayo AM, Mirama-Calderón LV, Vallejo-Ortega MT, Gaitán-Duarte HG. Effectiveness of treating gestational syphilis in the last trimester on the incidence of congenital syphilis: a systematic review and meta-analysis. Rev Colomb Obstet Ginecol. 2025;76(4):4268. doi: 10.18597/rcog.4268.
  8. Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1–187.
  9. Nlandu MV, Lewis EL, Carlson JM, et al. Evaluations and Treatment Among Infants Exposed to Syphilis in Utero, Six U.S. States, 2018-2021. J Pediatric Infect Dis Soc. 2026;15(3):piag011. doi: 10.1093/jpids/piag011.
  10. Barnes T, Girotto JE. The Role of Pediatric Pharmacists in the Prevention and Treatment of Congenital Syphilis. J Pediatr Pharmacol Ther. 2024;29(4):429–433.

 

 

Optimizing Care in Streptococcal Pharyngitis: Using Clinical Prediction Tools to Aid Antimicrobial Stewardship

By Megan McGrath PharmD Candidate,

Streptococcal pharyngitis is an infection caused by Streptococcus pyogenes (otherwise known as group A streptococcal or GAS). Children 3 to 14 years are most likely to have these infections with 93.2 cases per 1000 persons 3 to 9 years old and 40.9 cases per 1000 persons 10 to 18 years old.1 21.5% of all acute pharyngitis cases thought to be caused by GAS.1 GAS pharyngitis typically presents with a painful sore throat, swollen tonsils, and fever. Symptoms of cough and congestion instead suggest viral etiology.

Historically, the determination to test for streptococcal pharyngitis relied on clinical presentation and provider judgment. In recent years, however, clinical screening tools have been used more frequently to provide a validated score determining the likelihood of streptococcal pharyngitis.

Colonization with GAS in the throat is common in children; up to 20% may be asymptomatically colonized. Colonization rates decrease with age, with an estimated 5% of adults carrying GAS.2 The ideas is that screening tools can help prevent testing and thus reduce false positives from testing those colonized with GAS but not experiencing acute infection. The biggest issue with over-testing is that it can lead to unnecessary antibiotic prescribing, whereas appropriately testing patients with a high likelihood of GAS pharyngitis is important to prevent complications from the disease. Acute rheumatic fever, a rare complication of GAS pharyngitis, occurs in about 10 cases per 100,000 persons per year in the US, when antibiotics are either delayed or not utilized to treated GAS pharyngitis.3 The risk of this complication is higher in children (versus adults) and factors such as overcrowded living environment and limited healthcare access can further increase their risk.4

Streptococcal Pharyngitis Guideline Updates

In 2025, the Infectious Diseases Society of America(IDSA) released updated clinical practice guideline on GAS pharyngitis.5 This update focuses on risk assessment of streptococcal pharyngitis and determining the likelihood of infection requiring testing. It does not provide changes in disease treatment. The three main screening tools they discuss are Centor, McIsaac, and FeverPAIN, summarized below in Table 2.5 Each of these scoring rubrics consist of questions regarding a patients’ physical exam and clinical presentation compiled into a score to stratify the risk of the patient having GAS pharyngitis into a low (1-13%), moderate (21-38%) or high (51-69%) probability category.5 The tools are approved for use in patients greater than 3 years old with an onset of acute pharyngitis within the past 3 days. All 3 scoring systems evaluate absence of cough, tonsil appearance and presence of fever in their algorithms. Centor and McIsaac also evaluate presence of swollen or tender cervical lymph nodes.5-7 McIsaac was adapted from the Centor tool to be validated specifically in children and is the only tool that considers age with an added point for ages 3-14 years old. 5-7 These tools are most useful in identifying patients with a low probability of GAS infection who may not require testing. The McIsaac and Centro have more evidence as noted by a recent meta-analysis.

The guideline discussed that in the meta-analysis, McIsaac and Centor scoring were evaluated they were most useful for ruling out GAS infection than determining if the patient had the infection.5,8 So, if a child screens as low probability, testing is not recommended (negative predictive values with scores of 0 were 7.1 and 8.1%).5,8   Patients with moderate to high scores should undergo testing for GAS pharyngitis to ensure appropriate treatment and reduce the risk of complications.5

While clinical prediction tools can help to differentiate patients and reduce unnecessary testing, they also introduce the potential risk of missed GAS pharyngitis, which could increase the likelihood of progression to rheumatic fever if left untreated and infected with rheumatogenic strain.4 Although this risk is low, it is important to recommend to those who are not indicated for testing to return for additional evaluation if they do not improve in a few days to prevent significant delays in treatment.

Recommended Antibiotic Treatments

The IDSA GAS guidelines for recommended treatments have not been updated recently but are included for completeness.9  Most common treatments are outlined below with alternative options summarized in Table 1.9 First line treatments for streptococcal pharyngitis include:

       Penicillin or Amoxicillin as Firstline GAS Pharyngitis Treatment

  • Both meet antimicrobial stewardship principles of narrow spectrum and are low cost and easy for patients to access.
  • For young children, amoxicillin is the drug of choice due to its favorable taste and multiple available dosage forms (e.g., suspension, chewable, capsule)
  • Recommended amoxicillin dosing is different for GAS pharyngitis versus other infections it is amoxicillin 50 mg/kg/day divided in 1-2 daily doses (max 1000 mg/day) for 10 days.9

For GAS pharyngitis, due to the rare cases of rheumatic fever, it has been difficult to demonstrate if a shorter course would have the same benefit as 10 days, so at this point, the 10-day treatment duration continues to be recommended, despite many patients feeling better after about 3 days of treatment. Until there is new evidence or recommendations, GAS pharyngitis, remains one of the small number of conditions where it is still important to advise patients to complete their full antibiotic course.

Table 1: Alternative Antibiotic Agents for GAS Pharyngitis9-11

Antibiotic Agent Reason for Use
IM Penicillin G Benzathine
  • Technically considered a first-line treatment
  • Considered for those with significant vomiting, impaired oral intake, or adherence concerns (1 time dose)
  • Currently, availability is limited by manufacturer backorders and FDA product recalls. Thus, use may be restricted to specific populations and indications.
Cephalexin
  • Alternative for some penicillin allergic
  • Shares a similar side chain to amoxicillin- low cross sensitivity risk. Consider in patients with non-severe amoxicillin allergy.
Clindamycin
  • Alternative for penicillin and cephalosporin allergic
  • Since no similarity can be used in those with severe allergies
  • Increased cost and lack of preferred taste for liquid formulation are negatives that should be considered

Implications for Pharmacists

Pharmacists in ambulatory settings should be aware of these clinical screening tools to aid in their practice. Currently 8 states in the US allow pharmacists to test and treat for GAS pharyngitis independently, and many others permit this under collaborative practice agreements.12 When pharmacists bring these services into practice, the largest stewardship benefit is applying screening tools to best interpret which patients should be tested and thus limiting antibiotics prescribed to when most likely to provide benefit. It is about striking the right balance: avoiding unnecessary testing while still identifying patients early enough to intervene and prevent complications.  Additional research is needed to determine which clinical prediction tool will be the gold standard in practice. McIssac and Centor have been well validated, but FeverPAIN has less evidence, might be easier to implement, ease and convenience is important considerations for pharmacists working in a busy ambulatory setting. Incorporating these tools into practice can ensure patients are assessed appropriately with testing, treatment, and follow-up is consistently applied. When done correctly, implementation of these tools into practice is expected to potentially result in about 48% less inappropriate antibiotic treatments.6

Table 2: Summary of Clinical Prediction Tools for those > 3 years old (adapted from IDSA guideline) 5-7

Clinical Features Centor & McIsaac FeverPAIN
Duration of Symptoms Do not use rubric if symptoms longer than 3 days Symptom onset less than 3 days: 1 pt
Age McIsaac:                             Centor:

3-14: 1 pt                             n/a

15-44: 0 pt

>45: -1 pt

n/a
Physical Exam Swollen or purulent tonsils: 1 pt

Tender cervical lymph nodes: 1 pt

Swollen tonsils- 1 pt

Exudative tonsils- 1 pt

No Cough Yes, no cough: 1 pt Yes, no cough or cold: 1 pt
Fever (>100.4°F) Yes: 1 pt If yes in prior 24 hours: 1 pt

Score Interpretation: Low Risk: 0-1 = generally no testing; Moderate – High Risk: 2-5 = testing indicated

Megan McGrath is a Doctor of Pharmacy candidate at the University of Connecticut. This post was written as part of her Advanced Pharmacy Practice Experience under the guidance of her professor, Jennifer Girotto PharmD, BCPPS, BCIDP, who also reviewed and edited the piece.

References

  1. Lewnard JA, King LM, Fleming-Dutra KE, Link-Gelles R, Van Beneden CA. Incidence of pharyngitis, sinusitis, acute otitis media, and outpatient antibiotic prescribing preventable by vaccination against group A streptococcus in the united states. Clin Infect Dis. 2021;73(1):e47–e58. doi: 10.1093/cid/ciaa529.
  2. CDC. Transmission in and between facilities. Centers for Disease Control Web site. https://www.cdc.gov/group-a-strep/php/ltcf-toolkit/transmission.html. Updated 2025. Accessed February 19, 2026.
  3. Chowdhury MS, Koziatek CA, Tristram D, Rajnik M. Acute rheumatic fever. In: StatPearls. Treasure Island (FL): StatPearls Publishing LLC; 2025.
  4. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute streptococcal pharyngitis. Circulation. 2009;119(11):1541–1551. https://doi.org/10.1161/CIRCULATIONAHA.109.191959. doi: 10.1161/CIRCULATIONAHA.109.191959.
  5. Linder JA, Watson ME, Wessels MR, et al. 2025 clinical practice guideline update by the infectious diseases society of america on group A streptococcal (GAS) pharyngitis: Risk assessment using clinical scoring systems in children and adults. Clin Infect Dis. 2025. doi: 10.1093/cid/ciaf668.
  6. McIsaac WJ, White D, Tannenbaum D, Low DE. A clinical score to reduce unnecessary antibiotic use in patients with sore throat. CMAJ. 1998;158(1):75–83.
  7. Centor RM, Witherspoon JM, Dalton HP, Brody CE, Link K. The diagnosis of strep throat in adults in the emergency room. Med Decis Making. 1981;1(3):239–246. doi: 10.1177/0272989X8100100304.
  8. Willis BH, Coomar D, Baragilly M. Comparison of centor and McIsaac scores in primary care: A meta-analysis over multiple thresholds. Br J Gen Pract. 2020;70(693):e245–e254. doi: 10.3399/bjgp20X708833.
  9. Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the infectious diseases society of america. Clin Infect Dis. 2012;55(10):86. doi: 10.1093/cid/cis629.
  10. Bachmann LH, Stoner B. Bicillin L-A. Centers for Disease Control(CDC) Web site. https://www.cdc.gov/sti/php/from-the-director/2025-07-bicillin-recall.html. Updated 2025. Accessed February 19, 2026.
  11. Wheeler M. Penicillin G benzathine. American Society of Health-system Pharmacists(ASHP) Web site. https://www.ashp.org/drug-shortages/current-shortages/drug-shortage-detail.aspx?id=909. Updated 2026. Accessed February 19, 2026.
  12. NASPA. Pharmacist prescribing: Test and treat. https://naspa.us/resource/pharmacist-prescribing-for-strep-and-flu-test-and-treat/. Updated 2025. Accessed February 19, 2026.

 

 

How Long Should We Treat Pediatric Outpatient CAP? Rethinking Antibiotic Duration

By Nicole Pietraszewski PharmD Candidate,

Community acquired pneumonia (CAP) is the cause of about 1.5 million pediatric medical visits each year and remains the second-leading cause of pediatric hospitalizations in the United States.1 The 2011  Pediatric Infectious Disease Society and Infectious Diseases Society of America (PIDS/IDSA) guideline for pediatric CAP, currently archived, recommends a 10-day treatment course for most patients, as available evidence at the time supported that duration.2 Although the guideline acknowledged that shorter courses might be effective for uncomplicated outpatient cases and could help limit resistance, it has not been updated to reflect more recent data supporting shorter treatment durations.2

Importantly, the 2024 Report of the Committee on Infectious Diseases of the American Academy of Pediatrics (AAP Red Book)  currently recommends a 5-day treatment duration for uncomplicated CAP, while recognizing that longer courses remain appropriate for complicated infection.3 This guidance sets the stage for pharmacists to help standardize shorter, evidence-based CAP treatment durations across outpatient settings.

What do different guidelines recommend for pediatric outpatient CAP?

Other guidance has moved toward shorter (3-5 day) antibiotic courses for outpatient pediatric CAP.4,5 Both the World Health Organization (WHO) and the United Kingdom’s National Institute for Health and Care Excellence (NICE) published guidelines in 2024 and 2025, and respectively recommend this short duration.4,5

What evidence is there for short-duration treatment for pediatric outpatient CAP?

A large meta-analysis published compared short-duration treatment (3-5 days) versus long-duration treatment (5-10 days) antibiotic therapy in children (<18 years old) with CAP.1 The analysis included 16 randomized controlled trials, published from inception to April 30, 2022, with a total of 12,774 patients.1

Shorter antibiotic courses had similar outcomes as longer ones.1 There was no significant difference found in the odds of clinical cure (n=7,298; OR 1.01, 95% CI 0.87 to 1.17), risk of treatment failure which included generally worsening or non-improving illness requiring treatment change, hospitalization (n=10,303; RR 1.06, 95% CI 0.93 to 1.21), mortality (n=9,058; RD 0.0%, 95% CI -0.2 to 0.1), or adverse effects (n=2,249; RR 0.75, 95% CI 0.44 to 1.28).1 The subgroup analysis showed no differences by age, same or different drug class, and high or low income countries.1

A more focused CAP meta-analysis included all high-income country trials namely CAP-IT, SCOUT-CAP, SAFER, and the 2014 Greenberg trial.1,6 The meta-analysis, which is more applicable to US patients based on population and treatments, evaluated randomized controlled trials published from 2003 to 2022, concluded that 3-5 days was as safe and effective as 7-10 days in patients with uncomplicated CAP.6 It only included trials comparing beta-lactam therapies, consistent with PIDS/IDSA and AAP Red Book recommendations that amoxicillin is first-line for non-severe CAP.2,3,6

Populations of Focused CAP Meta-Analysis

This analysis found no difference between either treatment failure, defined as the need for antibiotic retreatment one month after initial course or hospitalization (n=1,541; RD -0.00, 95% CI -.03 to 0.02), or in adverse effects (n=1,194; RD -0.00, 95% CI -.05 to 0.05). 6

Overall, recent evidence supports 3 to 5 day beta-lactam treatment for children of at least 6 months old with uncomplicated CAP, primarily outpatient.

What does this mean for practice and what’s next?

Antimicrobial stewardship programs in the inpatient arena have demonstrated strong improvements in antimicrobial prescribing.  This strong evidence, specific to pediatric CAP, provides an opportunity for pharmacists in ambulatory settings (e.g., community, clinics, emergency departments) to improve review their current practice, and if warranted implement antimicrobial stewardship efforts to reduce routine prescribing to 3-5 day durations of amoxicillin for most pediatric outpatient CAP cases,

About the author: Nicole Pietraszewski, is a Doctor of Pharmacy candidate at the University of Connecticut. This post was written as part of her Advanced Pharmacy Practice Experience under the guidance of her professor, Jennifer Girotto PharmD, BCPPS, BCIDP, who also reviewed and edited the piece.

References

  1. Gao Y, Liu M, Yang K, et al. Shorter versus longer-term antibiotic treatments for community-acquired pneumonia in children: A meta-analysis. Pediatrics. 2023;151(6):e2022060097. doi: 10.1542/peds.2022–060097. doi: 10.1542/peds.2022-060097.
  2. Bradley JS, Byington CL, Shah SS, et al. Executive summary: The management of community-acquired pneumonia in infants and children older than 3 months of age: Clinical practice guidelines by the pediatric infectious diseases society and the infectious diseases society of america. Clin Infect Dis. 2011;53(7):617–630. doi: 10.1093/cid/cir625.
  3. Systems-based treatment tableCommittee on Infectious Diseases, American Academy of Pediatrics, Kimberlin DW, Banerjee R, Barnett ED, Lynfield R, Sawyer MH, eds. Red book: 2024–2027 report of the committee on infectious diseases. American Academy of Pediatrics; 2024:0. https://doi.org/10.1542/9781610027373-TAB. Accessed 2/9/2026. 10.1542/9781610027373-TAB.
  4. World Health Organization. Guideline on management of pneumonia and diarrhoea in children up to 10 years of age. 2024. https://iris.who.int/server/api/core/bitstreams/bddcc725-8ffd-4d38-bec4-d6ead2904911/content.
  5. National Institute for Health and Care Excellence. Pneumonia: Diagnosis and
    management. 2025.
  6. Kuitunen I, Jääskeläinen J, Korppi M, Renko M. Antibiotic treatment duration for community-acquired pneumonia in outpatient children in high-income countries-A systematic review and meta-analysis. Clin Infect Dis. 2023;76(3):e1123–e1128. doi: 10.1093/cid/ciac374.
  7. Bielicki JA, Stöhr W, Barratt S, et al. Effect of amoxicillin dose and treatment duration on the need for antibiotic re-treatment in children with community-acquired pneumonia: The CAP-IT randomized clinical trial. JAMA. 2021;326(17):1713–1724. doi: 10.1001/jama.2021.17843.
  8. Williams DJ, Creech CB, Walter EB, et al. Short- vs standard-course outpatient antibiotic therapy for community-acquired pneumonia in children: The SCOUT-CAP randomized clinical trial. JAMA Pediatr. 2022;176(3):253–261. doi: 10.1001/jamapediatrics.2021.5547.
  9. Pernica JM, Harman S, Kam AJ, et al. Short-course antimicrobial therapy for pediatric community-acquired pneumonia: The SAFER randomized clinical trial. JAMA Pediatr. 2021;175(5):475–482. doi: 10.1001/jamapediatrics.2020.6735.
  10. Greenberg D, Givon-Lavi N, Sadaka Y, Ben-Shimol S, Bar-Ziv J, Dagan R. Short-course antibiotic treatment for community-acquired alveolar pneumonia in ambulatory children: A double-blind, randomized, placebo-controlled trial. Pediatr Infect Dis J. 2014;33(2):136–142. doi: 10.1097/INF.0000000000000023.

 

 

Surgical Infection Society Pediatric Intra-Abdominal Infection – Antimicrobial Stewardhip Highlights

The Surgical Infection Society (SIS) Guidelines on the Prevention and Management of Pediatric Intra-Abdominal Infection Update was just published.1 These authors note that these are to be used in conjunction with the prior guidelines, as many aspects have not changed. Source control remains essential. For treatment they continue to recommend the combination of ceftriaxone (or cefotaxime, if available) with metronidazole or monotherapy with ertapenem for lower-risk infants, children, and adolescents. After achievement of source control, antibiotic duration in patients beyond the neonatal period (i.e., > 45 weeks post conceptional age), should be limited to 5 days.1 In cases of perforated appendicitis complicated by post-operative abscess, the guideline recommends antibiotic duration should not exceed 7 days. Therapy should be transitioned to oral agents with high bioavailability as early as feasible.  The guidelines also discuss risk categories, although their definition includes some elements that are adult focused (e.g., advanced age), most of the high-risk features (e.g., septic shock, delayed or inadequate source control, post-operative intra-abdominal infections, multiple medical comorbidities or cancer, those with a history of a multi-drug resistant organism) are directly applicable to the pediatric population.1

What is currently recommended for treatment of intra-abdominal infections per SIS?

How should we treat infants?

The guidelines made specific recommendations for the treatment of two groups of infants. The first was preterm infants.1 This is based on findings of no differences reported in clinical outcomes from an open label, multicenter trial that included infants (n=180) that were ≤ 33 weeks gestational age and <121 days old.1,2 The antibiotic regimens included in the study and recommended for preterm infants with intra-abdominal infection (primarily necrotizing enterocolitis) are: ampicillin and gentamicin with either metronidazole or clindamycin or piperacillin-tazobactam with gentamicin.1,2  Although the first 2 regimens are standard, the rational for the study combining gentamicin with the piperacillin-tazobactam, resulting in dual Gram-negative coverage, is not entirely clear.  The second infant recommendation is that metronidazole is the anti-anaerobic agent of choice for combination therapy in infants.1 This recommendation was based on a multicenter open label trial that included infants of ≥34 weeks gestational age and < 121 days old.1,3 All patients received metronidazole as part of their intra-abdominal infection treatment. The panel cited high overall cure rates (98%) along with low rates of death (2%), intestinal perforation (2%), and intestinal stricture (2%).1,3

What about empiric treatment of older infants, children and adolescents

For empiric therapy of intra-abdominal infection in older pediatric patients.1 The guidelines recommend having antimicrobial stewardship protocols in place to help improve appropriateness of antibiotic choice. Data further suggest that enterococcal specific targeted therapy is not needed.

For empiric choices of antibiotics in those with low-risk disease, they recommend ceftriaxone (or cefotaxime, where available) both in combination with metronidazole or monotherapy with ertapenem.1 In patients who meet high-risk criteria the guidelines did add the broad-spectrum cephalosporin-beta-lactamase combinations: ceftolozane/tazobactam and ceftazidime-avibactam based on small outcome studies used to obtain pediatric FDA approval for intra-abdominal infections.1,4,5 Note that the guidelines suggest, and antimicrobial stewardship principles strongly recommend protecting and reserving these agents when the patient is at high risk, such as those with known resistance to usual agents.1

Antimicrobial therapy the SIS guidelines recommend against moxifloxacin for empiric therapy.1,6  This recommendation authors note was due to a combination of increased rate of antibiotic attributed adverse effects (14% vs 7%) and lower cure rates (85% vs 96%).1,6

What are the recommendations for perforated appendicitis?

Different antibiotics (i.e., piperacillin-tazobactam or ertapenem) are recommended by the SIS for perforated appendicitis.1  The panel did not endorse the use of ceftriaxone and metronidazole for perforated appendicitis, comparing the 2 in pediatrics. The IMPACT study found that piperacillin-tazobactam had significantly lower rates of post-operative intra-abdominal abscesses (6% vs 24%), need for post-op CT scanning (14% vs 30%), emergency department visits (9% vs 26%).1,7 Further, authors reported the choice of medication was most significant predictor of the intra-abdominal post-operative abscess formation.1,7 However, the evidence is not entirely one-sided. A 2025 meta-analysis published after the SIS pulled their study data, incorporating the IMPPACT trial and 3 retrospective studies did not find significant differences between antibiotic regimens. Because 3 of the 4 studies were observational, there is some concern for selection bias.8  As such, the question may still be up for debate.

The randomized study supporting ertapenem’s inclusion, compared it versus gentamicin and metronidazole, a regimen not commonly used for pediatric perforated appendicitis in the US.1,9 While patients who received the ertapenem became afebrile 2 days sooner, no differences were reported for other clinical outcomes.1,9 This study is important, but also raises some generalizability questions about how it compares to currently used regimens.

That said, the evidence in this area remains nuanced.  It will be interesting to see how the upcoming Infectious Diseases Society of America intra-abdominal infection guidelines update addresses these same questions.

When can therapy be transitioned to PO?

Data support transitioning from intravenous to oral therapy once source control is achieved in pediatric patients with perforated disease.1 In the pediatric studies supporting this recommendation, commonly used oral antibiotics included amoxicillin/clavulanate monotherapy or trimethoprim/sulfamethoxazole with metronidazole.1

Key Stewardship Takeaways

This update to the SIS recommendations for pediatric patients with intra-abdominal infections summarizes the current literature and highlights the importance of antimicrobial stewardship including having established protocols, choice of antimicrobial therapy, and evidence-based transition to oral therapy for pre-determined durations.  Although there are nuanced considerations, overall, it provides guidance to help support improved patient care in this area.

References

  1. Huston JM, Forrester JD, Barie PS, et al. Surgical Infection Society Guidelines on the Prevention and Management of Pediatric Intra-Abdominal Infection: 2025 Update. Surg Infect (Larchmt). 2026;27(1):5–15.
  2. Smith MJ, Boutzoukas A, Autmizguine J, et al. Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections. Pediatr Infect Dis J. 2021;40(6):550–555.
  3. Commander SJ, Gao J, Zinkhan EK, et al. Safety of Metronidazole in Late Pre-term and Term Infants with Complicated Intra-abdominal Infections. Pediatr Infect Dis J. 2020;39(9):e245–e248.
  4. Bradley JS, Broadhurst H, Cheng K, et al. Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children ≥3 Months to <18 Years With Complicated Intra-Abdominal Infection: Results From a Phase 2, Randomized, Controlled Trial. >Pediatr Infect Dis J. 2019;38(8):816–824.
  5. Jackson CA, Newland J, Dementieva N, et al. Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection. Pediatr Infect Dis J. 2023;42(7):557–563.
  6. Wirth S, Emil SGS, Engelis A, et al. Moxifloxacin in Pediatric Patients With Complicated Intra-abdominal Infections: Results of the MOXIPEDIA Randomized Controlled Study. Pediatr Infect Dis J. 2018;37(8):e207–e213.
  7. Lee J, Garvey EM, Bundrant N, et al. IMPPACT (Intravenous Monotherapy for Postoperative Perforated Appendicitis in Children Trial): Randomized Clinical Trial of Monotherapy Versus Multi-drug Antibiotic Therapy. Ann Surg. 2021;274(3):406–410.
  8. Armstrong J, Sriranjan J, Briatico D, et al. Piperacillin/tazobactam versus ceftriaxone/metronidazole for children with perforated appendicitis: a systematic review and meta-analysis. Pediatr Surg Int. 2025;42(1):3–z.
  9. Pogorelić Z, Silov N, Jukić M, et al. Ertapenem Monotherapy versus Gentamicin Plus Metronidazole for Perforated Appendicitis in Pediatric Patients. Surg Infect (Larchmt). 2019;20(8):625–630.

 

Measles is Back, What Should You Know?

Measles, a disease that was a rare occurrence in the recent past, has become much more common beginning in 2025. As I have received many questions about measles vaccine and treatment options, I thought it would be a good initial topic to discuss in early 2026.

Measles Cases Continuing to Increase

The incidence of measles in the US and many developed countries has been on the rise. In 2025 the US, the Centers for Disease Control and Prevention have noted 2276 cases in 44 states.1 Most cases (68%) were in children, and the youngest children (<5 years old) have the highest rates of hospitalization (20%).1 In early 2026, these increases continue with 733 cases by February 5, 2026.1

Measles Vaccine is Very Effective

The measles, mumps, and rubella (MMR) vaccine is a very effective live attenuated vaccine.  One dose of MMR is about 90% effective and 2 doses 97%.2,3  Without appropriate immunity (primarily obtained from vaccination), measles is very contagious, causing disease in more than 90% of exposed individuals.3

MMR vaccination is routinely recommended as a 2-dose series (dose 1 at 12-15 months of age, dose 2 at 4-6 years).4-6 Doses as close as 28 days apart are considered valid.  The MMR vaccine is also recommended for susceptible individuals as young as 6 months of age during an outbreak (consult local public health for specifics) or in those planning international travel (doses given prior to 12 months of age do not count towards 2 routine dose recommendation).7,8

How does measles disease present?

Measles has an initial prodrome when symptoms can be similar to a severe cold or flu with fever (often high), cough, runny nose, and conjunctivitis.3,7 The characteristic Koplik spots may be present during the prodrome or may become present a day or two later. The rash, which begins in the head/facial area and spreads downward has been one of the most obvious symptoms of measles, does not present until 2-5 days into the illness. Thus, besides being very contagious, another reason patients transmit it to others is they may not think they have measles while they are most contagious. In healthy individuals, the infectious period is 4 days before and 4 days after the rash appears.3,7

Measles can have complications and infants and young children are at risk for these. The most common complications include diarrhea, ear infections and pneumonia.3 Important, but rare complications include acute encephalitis as well as a late onset (7-10 years later) fatal complication of subacute sclerosing panencephalitis.3

What can I do if susceptible children are exposed?

Vaccines and measles immunoglobulin can be helpful at protecting exposed patients, if the patient is aware and can obtain it in time. The vaccine is the preferred recommendation (84 – 100% effectiveness) in non-immune eligible patients (i.e., ≥ 6 months and without contraindications) who were exposed in the prior 72 hours.7,9 Immune globulin is recommended (76-100% effectiveness) for those who have a risk factor and are unable to receive the vaccine due to age (e.g., < 6 months), timing (e.g., > 72 hours but < 5 days), or contraindication to the vaccine (e.g., immunocompromise, pregnancy).7,9

Are there any treatments for measles?

There are no antivirals that have efficacy against measles.  Data from a 2025 Cochrane review on the use of vitamin A for the treatment of measles, relied on limited studies published in the 1980’s and 1990’s.10 In their review of the studies they found that two doses of vitamin A at 200,000 IU did not result in overall lower risk of mortality; however, it was associated with lower mortality in young children (e.g., < 2 years) and in those who had measles associated pneumonia.10 It also had a slight reduction in measles croup.  The vitamin A was not, however, effective at preventing pneumonia and had only a non-significant impact on the duration of pneumonia.10

Summary

It is important to make sure that all are aware that measles is preventable by a highly effective routine immunization recommended in childhood.  Catch-up vaccination can be given to all those without protection as long as they do not have any contraindications.  When individuals contract measles disease there are no specific treatments, although a 2-dose series of vitamin A may help in some circumstances.

References

  1. Centers for Disease Control and Prevention. Measles Cases and Outbreaks. Accessed February 6, 2026https://www.cdc.gov/measles/data-research/
  2. Paul Gastanaduy, Penina Haber, Paul Rota, Manisha Patel. Chapter 13: Measles. In: Elisha Hall, A. Patricia Wodi, Jennifer Hamborsky, Valerie Morelli, Sarah Schille, eds. The Epidemiology and Prevention of Vaccine-Preventable DiseasesPublic Health Foundation; 2024
  3. James L. Goodson and Thomas D. Filardo. Measles (Rubeola). In: Centers for Disease Control and Prevention (CDC), ed. CDC Yellow Book 2026: Health Information for International Travel.2026th ed. https://www.cdc.gov/yellow-book/hcp/travel-associated-infections-diseases/measles-rubeola.html
  4. American Academy of Family Physicians. Immunization Schedules. Accessed December 12, 2025 https://www.aafp.org/family-physician/patient-care/prevention-wellness/immunizations-vaccines/immunization-schedules.html
  5. American Academy of Pediatrics, Committee on Infectious Diseases. Red Book : Report of the Committee on Infectious Diseases 2024 – 2027. AAP Immunization Schedule. Accessed December 12, 2025 https://publications.aap.org/redbook/resources/15585/AAP-Immunization-Schedule
  6. Centers for Disease Control and Prevention. Child and Adolescent Immunization Schedule by Age (Addendum updated August 7, 2025). Accessed September 20, 2025 https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html
  7. Committee on Infectious Diseases, American Academy of Pediatrics. Measles. In: David W Kimberlin, Ritu Banerjee, Elizabeth D Barnett, Ruth Lynfield, Mark H. Sawyer, eds. Red Book: 2024–2027 Report of the Committee on Infectious Diseases (33rd Edition) American Academy of Pediatrics; 2024
  8. Mathis AD, Raines K, Filardo TD, et al. Measles Update – United States, January 1-April 17, 2025. MMWR Morb Mortal Wkly Rep. 2025;74(14):232–238
  9. Montroy J, Yan C, Khan F, et al. Post-exposure prophylaxis for the prevention of measles: A systematic review. Vaccine. 2025;47:126706
  10. Huiming Y, Chaomin W, Meng M. Vitamin A for treating measles in children. Cochrane Database Syst Rev. 2005;2005(4):CD001479

Pediatric Bacterial Arthritis (Septic Arthritis): Takeaways for Pharmacy Practice (with additional data supporting oral therapy for some)

By Kenna Riley PharmD Candidate,  

Bacterial arthritis (e.g., septic arthritis) is caused by bacteria entering the joint from the bloodstream, causing infection and inflammation of the joint and synovial fluid.​1​ It requires prompt antibiotic treatment to prevent severe outcomes, such as irreversible joint damage.  In 2023, the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) published a guideline to provide recommendations on diagnosis and treatment strategies to improve patient outcomes.1 The purpose of this writing is to summarize the key points in that guideline and summarize any emerging data.

Antimicrobial Recommendations

Bacterial arthritis generally affects a single joint (e.g., knee) and presents with sudden onset fever, joint pain, swelling, and immobility.​1​ Those who are most at risk include children under 3 years, males, those with recent trauma, and individuals with a weakened immune system (e.g., prematurity, sickle cell disease, or HIV).​1​To improve the likelihood of identifying a pathogen, it is recommended, when clinically reasonable, to obtain a full work up (e.g., blood culture, synovial fluid culture/analysis, C-reactive protein, imaging) prior to the initiation of empiric antibiotics.​1

Staphylococcus aureus is the most common cause of bacterial arthritis in children.​1Kingella kingae is another causative pathogen, that has up until recently been unable to be identified, but with recent technology with improved diagnostics this is now feasible.2​​ K. kingae is most commonly seen in children 6 months to 5 years old.1,2 These two pathogens luckily is often present a bit differently. When bacterial arthritis is caused by S. aureus it typically has a rapid and aggressive onset, with joint pain that quickly worsens over 24 to 48 hours.​1,2 Whereas K. kingae infections have a more gradual onset with symptoms at presentation often being less severe.​​2

 

Treatment of Bacterial Arthritis

PIDS/IDSA guidelines recommend empiric therapy to cover S. aureus.1​ It is important to consider pediatric methicillin-resistant S. aureus (MRSA) rates, especially community-associated MRSA as these vary by region. In areas with low MRSA prevalence (e.g., <10-15% of community-acquired S. aureus infections), guidelines recommend empiric treatment with either a first-generation cephalosporin (e.g., cefazolin) or an anti-staphylococcal penicillin (e.g., nafcillin, oxacillin).1  In contrast, in regions with high MRSA prevalence, it’s essential to empirically include an agent with strong MRSA activity, such as clindamycin (if high rates of susceptibility) or vancomycin.​​ In those who are 6 months to less than 4 years old, it is suggested to ensure coverage also includes K. kingae (which is already covered if cefazolin is chosen) by adding an agent such as ampicillin to either clindamycin or vancomycin therapies.​1

When choosing an antibiotic, it’s important to understand each antibiotic’s risks vs benefits. Starting with the antibiotics used in areas with lower MRSA rates. Penicillins and cephalosporins are time-dependent killing drugs and efficacy is best predicted by the amount of time the antibiotic’s concentration remains above the minimum inhibitory concentration (T>MIC). The anti-staphylococcal penicillins require frequent administration every 4 to 6 hours and are associated with adverse effects such as phlebitis, interstitial nephritis, as well as hematologic suppression (e.g., anemia, neutropenia) when used for longer periods (e.g., > 14 days). In contrast, cefazolin offers a more convenient dosing schedule, administered every 8 hours, while still maintaining a strong safety profile and efficacy against MSSA and K. kingae.​

Another key antibiotic often used in treatment, particularly for suspected methicillin-resistant S. aureus (MRSA) infections, is vancomycin. This is a good first choice when highly reliable MRSA coverage is needed. Vancomycin is the preferred antimicrobial agent for clindamycin-resistant CA-MRSA infections when initial parenteral therapy is required.1 It requires therapeutic drug monitoring due to its narrow therapeutic index and nephrotoxicity risk. On the other hand, clindamycin is a great alternative with excellent oral bioavailability, making it optimal when susceptible, especially for outpatient management. However, clindamycin resistance may be a concern, depending on the local resistance rates and must be weighed into decision making. Ultimately, the choice between these two agents is determined by the severity of the infection, local susceptibility rates, and the need to balance their risks and benefits.

It is also important to note that the guidelines do not recommend the use of adjunctive corticosteroids. There is insufficient evidence to support their benefit, and they may suppress the immune system, hindering the body’s ability to clear the infection.

In addition to what therapies to use and avoid, therapy duration is another important consideration.  The guidelines state that the total duration of therapy is variable and depends on a patient’s clinical and laboratory response to treatment, as well as the specific pathogen. For patients who show rapid clinical improvement and a trending decrease in C-reactive protein (CRP) by the end of the first treatment week, a shorter course of 10 to 14 days is often sufficient.1 However, if a patient has a slower clinical response, has inadequate source control, or has persistently elevated CRP levels, a longer course of 21 to 28 days may be preferred to ensure the infection is completely cleared.​1 This approach allows for adjustments in therapy duration as the patient’s condition evolves, ensuring both efficacy and patient safety.

Areas of Uncertainty & Emerging Evidence

While the new guideline provides a strong framework, it also highlights areas of clinical uncertainty. Future research is needed to improve the diagnostic accuracy of laboratory tests, better define the role of advanced molecular pathogen identification, and establish an optimal duration for antibiotic therapy. These gaps underscore that while guidelines are a vital resource, they also serve as a road map for future research to refine and improve the care of children with septic arthritis.

The 2023 PIDS/IDSA guidelines for pediatric acute bacterial arthritis are recently published and there has been limited new evidence that would significantly result in many changes. A notable study was published in 2024 that supports initial oral therapy.   A nationwide, randomized controlled trial from September 2020 to June 2023 in Denmark evaluated non-severe uncomplicated bone and joint infections (~40% were joint infections) comparing initial therapy of intravenous ceftriaxone 100 mg/kg/day once daily or oral therapy with amoxicillin/clavulanate 100/12.5 mg/kg/day in three daily doses in children 3 months to 5 years or dicloxacillin 200 mg/kg/day in four daily doses in children 5 to 17 years.  Patients in both groups were changed to standard dose oral therapy after at least 3 days of therapy and demonstration of clinical and laboratory improvement.  Approximately 40% of the patients had joint infections with 25% identifying a specific pathogen (S. aureus 14-16% – only 1 of which had MRSA and K. kingae 5-9%).  Total duration of antibiotics for joint infections were 12.6 (10.3 – 19.4) high dose oral therapy and 10.6 (9.8-14.2) days initial intravenous therapy.  No patients met the study designed criteria of sequelae after 6 months demonstrating non-inferiority of the high-dose oral therapy. With regards to adverse effects nausea was statistically higher in those in the high dose oral therapy group (11.2% vs 2.5%).  No serious complications were noted.3 This study provides some additional prospective evidence that intravenous therapy may not always be necessary for treatment of MSSA and K. kingae bone and joint infections in children.

 

About the author: Kenna Riley is a Doctor of Pharmacy candidate at the University of Connecticut. This post was written as part of her Advanced Pharmacy Practice Experience under the guidance of her professor, Jennifer Girotto PharmD, BCPPS, BCIDP, who also reviewed and edited the piece.

References

​​1. Woods CR, Bradley JS, Chatterjee A, et al. Clinical practice guideline by the pediatric infectious diseases society (PIDS) and the infectious diseases society of america (IDSA): 2023 guideline on diagnosis and management of acute bacterial arthritis in pediatrics. J Pediatric Infect Dis Soc. 2024;13(1):1–59. doi: 10.1093/jpids/piad089.

​3. Gouveia C, Duarte M, Norte S, et al. Kingella kingae displaced S. aureus as the most common cause of acute septic arthritis in children of all ages. Pediatr Infect Dis J. 2021;40(7):623–627. doi: 10.1097/INF.0000000000003105.

​4. Nielsen AB, Holm M, Lindhard MS, et al. Oral versus intravenous empirical antibiotics in children and adolescents with uncomplicated bone and joint infections: A nationwide, randomised, controlled, non-inferiority trial in denmark. Lancet Child Adolesc Health. 2024;8(9):625–635. doi: 10.1016/S2352-4642(24)00133-0.

​​

 

What You Need to Know About Influenza Disease in Children in 2025

Influenza Disease and Vaccination

Influenza activity has been increasing for the past few weeks. Centers for Disease Control and Prevention (CDC) influenza surveillance week 50 shows increasing influenza with children especially impacted.  Influenza-like illness last week, was highest in those 0-4 years (11.2%) followed by 5–24-year-olds (7.5%).1 Emergency department visits for influenza were also significant youth accounting for 9.2% of 5-17 year-old visits and 7% of visits for those 0-4 years-old.1

Among typed influenza viruses, about 90% are influenza A (H3N2), predominantly the drifted clade 2a.3a.1 subclade K.1  As you have likely heard, the subclade K is a drifted variant and thus not optimally matched to the H3N2 strain included in the 2025-2026 influenza vaccine.1 Despite the mismatch, vaccine effectiveness against severe disease and outcomes in pediatrics appears strong. Preliminary data from the United Kingdom suggest that the vaccine has 74.7% (95% CI 52.3 – 87.9) effectiveness against emergency department visits and 72.8% (95% CI 48.3-87.1) effectiveness against hospital admission in children 2-17 years, respectively.2  These findings reinforce the role of influenza vaccination in preventing severe disease in children.

Unfortunately, pediatric influenza vaccination rates are concerningly low with only 40.8% of US children currently vaccinated against influenza.3  Pharmacists play a critical role in educating parents, addressing vaccine hesitance, and reinforcing that vaccination remains important throughout the influenza season.

Key influenza vaccine points to remember4-6:

  • The only way to protect children < 6 months of age is via maternal immunization at least 2 weeks prior to delivery.
  • Children 6 months to ≤ 9 years who have not previously received 2 doses of influenza vaccine, require 2 doses this season, separated by ≥ 28 days.
  • Other patients should receive 1 dose of influenza vaccine this year.
  • Protective immunity takes about 2 weeks (for those needing 2 doses, the 2-week count begins after the second dose).

Influenza Treatment Recommendations

If children become sick with influenza, it is important to ensure they receive guideline recommended treatments.  Data from 2023-2024 US influenza season indicate substantial underutilization of anti-influenza therapy in pediatric patients. Only 31% pediatric outpatients and 52-59% hospitalized pediatric patients with influenza received recommended treatment.7 Clinician surveys using pediatric case scenarios highlight gaps in guideline adherence.  In March – June 2024, two surveys (1 outpatient and 1 inpatient) with clinical pediatric influenza cases was sent to prescribers in 7 children’s hospitals and their affiliated community hospitals.8,9  In the outpatient analysis, clinicians generally only recommended treatment for one of the three recommended cases.9 Approximately 50% of inpatient providers recommended therapy for the hospitalized pediatric influenza cases (32% – 59%, depending on the case).8  In both studies, pediatric infectious diseases physicians were most likely to choose oseltamivir treatment, with the generalists (e.g., pediatric primary care or hospitalists) least likely.8,9

Importantly, the CDC reports that anti-influenza treatments (e.g.,  neuraminidase inhibitors, PA Cap-Dependent Endonuclease Inhibitor) continue to be effective against the circulating strains, including H3N2 subclade K.1  The Infectious Diseases Society of America, American Academy of Pediatrics, and Centers for Disease Control and Prevention all recommend prompt treatment with oseltamivir, regardless of duration of symptoms for all patients with high risk conditions.

Pediatric Patients that are at high risk and should receive treatment with oseltamivir, regardless of duration of symptoms: 10-12

  • All < 2 years of age per CDC 11 or < 5 years of age AAP 12;
  • All with underlying conditions that increase risk for complications,
  • All with severe, complicated, or progressing disease,
  • All who are hospitalized with influenza disease.

Consider those with uncomplicated disease who present within 48 hours of symptoms may receive antiviral treatment with any of the neuraminidase inhibitors (i.e., oseltamivir, zanamivir, peramivir) or baloxavir, that are age appropriate (see Table 1).11,12

Pediatric Specific Outcome Data

Outcome data for anti-influenza treatment in pediatric patients are limited.  Available evidence suggests benefits in prompt treatment of pediatric patients in the outpatient and hospital settings.   Walsh and colleagues evaluated the impact of prompt anti-influenza treatment in pediatric patients hospitalized with influenza.13  They included almost 56,000 pediatric patients from multiple centers from 2007 – 2020 in a retrospective analysis.  Those who received prompt oseltamivir within day 0-1 of hospitalization had reduced length of stay, decreased 7-day hospital readmission, and lower risk of ECMO use/death compared to those who received delayed or no oseltamivir treatment.13 In the outpatient setting, an individual patient meta-analysis was performed including 5 trials and 2,561 pediatric patients who were randomized to receive oseltamivir or placebo within 48 hours of symptom onset.14  Oseltamivir reduced symptom duration by 17.6 hours (0.7 – 34.5 hours) and had a 34% risk reduction in acute otitis media infections. An increase in vomiting was found in those that received oseltamivir (RR 1.63 (95% CI 1.3-2.04).14

Pharmacists Role

With the increasing influenza disease activity, pharmacists have an essential role to ensure parents understand the importance and effectiveness of the influenza vaccination.  In addition, cases of clinical influenza disease provides an antimicrobial stewardship opportunity to recommend appropriate anti-influenza therapy in high-risk pediatric patients.

 

Table 1.  Anti-Influenza Medications for Treatment of Influenza Disease11,15

Medication FDA approval ages for treatment Notes
Oseltamivir (Tamiflu®) ≥ 14 days-old (any age) Intermittent shortage reported for some manufacturers as of Dec 2025
Zanamivir (Relenza®) ≥ 7 years-old Do not use in those with respiratory disease or lactose/milk protein allergy
Peramivir (Rapivab™) ≥ 6 months-old
Baloxavir (Xofluza®) ≥ 5 years Do not crush tablets, instead use suspension packets in those < 20 kg or who cannot take tablets. Not recommended as monotherapy for immunocompromised

    References

    1. Centers for Disease Control and Prevention. FluView:Weekly US Influenza Surveillance Report. Accessed December 23, 2025https://www.cdc.gov/fluview/surveillance
    2. Kirsebom FC, Thompson C, Talts T, et al. Early influenza virus characterisation and vaccine effectiveness in England in autumn 2025, a period dominated by influenza A(H3N2) subclade K. Euro Surveill. 2025;30(46):2500854. doi: 10.2807/1560
    3. Centers for Disease Control and Prevention. FluVaxView. Accessed Deccember 23, 2025. Available at: https://www.cdc.gov/fluvaxview/dashboard/vaccine-doses-distributed.html
    4. American Academy of Pediatrics, Committee on Infectious Diseases. Red Book : Report of the Committee on Infectious Diseases 2024 – 2027. AAP Immunization Schedule. Accessed December 12, 2025. Available at: https://publications.aap.org/redbook/resources/15585/AAP-Immunization-Schedule
    5. American Academy of Family Physicians. Immunization Schedules. Accessed December 12, 2025. Available at: https://www.aafp.org/family-physician/patient-care/prevention-wellness/immunizations-vaccines/immunization-schedules.html
    6. Centers for Disease Control and Prevention. Child and Adolescent Immunization Schedule by Age (Addendum updated August 7, 2025). Accessed September 20, 2025. Available at: https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html
    7. Frutos AM, Ahmad HM, Ujamaa D, et al. Underutilization of Influenza Antiviral Treatment Among Children and Adolescents at Higher Risk for Influenza-Associated Complications – United States, 2023-2024. MMWR Morb Mortal Wkly Rep. 2024;73(45):1022–1029
    8. Bassett HK, Rao S, Beck J, et al. Variability of Clinician Recommendations for Oseltamivir in Children Hospitalized with Influenza. Pediatrics. 2025;155(5):e2024069111. doi: 10.1542/peds.2024–069111
    9. Bassett HK, Rao S, Beck J, et al. Clinician Preferences for Oseltamivir Use in Children With Influenza in the Outpatient Setting. Pediatrics. 2025;156(3):e2025071193. doi: 10.1542/peds.2025–071193
    10. Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis. 2019;68(6):895–902
    11. Centers for Disease Control and Prevention. Influenza Antiviral Medications: Summary for Clinicians. Accessed December 23, 2025. Available at: https://www.cdc.gov/flu/hcp/antivirals/summary-clinicians.html
    12. Committee on Infectious Diseases. Recommendations for Prevention and Control of Influenza in Children, 2025-2026: Policy Statement. Pediatrics. 2025;156(6):e2025073620. doi: 10.1542/peds.2025–073620
    13. Walsh PS, Schnadower D, Zhang Y, et al. Association of Early Oseltamivir with Improved Outcomes in Hospitalized Children with Influenza, 2007-2020. JAMA Pediatr. 2022;176(11):e223261
    14. 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
    15. Michelle Wheeler. ASHP Drug Shortages – Current Shortages. Accessed December 23, 2025. Available at: https://www.ashp.org/drug-shortages/current-shortages/drug-shortage-detail.aspx?id=881&loginreturnUrl=SSOCheckOnly