By Marissa Galicia, PharmD candidate

Multidrug-resistant organisms (MDROs) represent a threat to global health, causing infections that are difficult to treat due to resistance to multiple antimicrobial classes. Some preventable ways that MDROs develop are when antibiotics are used longer than necessary or taken inappropriately.¹ Initially, only a few bacteria may survive antibiotic treatment, but frequent or inappropriate use increases the likelihood of resistant bacteria surviving and causing infections. Rising resistance rates, emphasizing the urgency of optimizing treatment strategies for pediatric populations.¹

Antibiotic Susceptibility in Children’s Hospitals Across the United States

In a 2025, Markham and colleagues published a multicenter analysis of antibiograms from 46 U.S. children’s hospitals.²   Most isolates in these hospitals remained susceptible with about 65% of Staphylococcus aureus was methicillin susceptible and 80% susceptible to clindamycin. Among Gram-negative bacteria, there was high susceptibility to cefazolin.²  For Gram-negatives greater than 85% E. coli and 78% Klebsiella sp. were susceptible to cefazolin.  Although many of these isolates were susceptible, resistance does sometimes occur.  Thirty-five percent of Staphylococcus aureus isolates and 57% of coagulase negative staphylococcus were resistant to oxacillin.   Almost 6% of E. coli, 9% of Klebsiella sp., and 17% of Serratia sp. resistant to ceftriaxone [possibly a signal for a possible extended spectrum beta-lactamase (ESBL) producer or other multidrug resistance (MDR) mechanism].  Enterobacter is generally thought to be resistant to ceftriaxone, regardless of the reporting, but in this study almost 6% were also resistant to ertapenem.  Cefepime, meropenem, and piperacillin-tazobactam, common anti-pseudomonas therapies each were reported to have about 10% pseudomonal resistance.  Lastly, and a bit concerningly 17% of Acinetobacter sp. were listed with meropenem resistance.²

In recent years, the Infectious Diseases Society of America has published recommendations for treatment of MDR infections.³  This includes the treatment of some important Gram-negative resistances such as Carbapenem-resistant Enterobacterales (CRE), Carbapenem-resistant Acinetobacter, Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E), and multidrug-resistant (MDR) Pseudomonas aeruginosa.  As a pharmacist, it is essential to consider the significant differences that often exist in pediatric and adult pharmacokinetics (e.g., increased distribution, increased clearance) these can impact on likelihood of attaining pharmacodynamic targets.⁴,  Thus the dose becomes as important as the choice of agents. A group that included pediatric infectious diseases physician and pharmacist experts published consensus recommendations for the dosing of select beta-lactam agents used to treat these antimicrobial-resistant Gram-negative infections in children.⁵ This review focuses on the treatment of these MDROs, which may be uncommon, but important infections in pediatrics (with dosing considerations for older children and adults).

Types of Resistance Impacting Enterobacterales

ESBLs enzymes inactivate most penicillins, cephalosporins, and aztreonam. When present, they are most frequently seen in Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis.³  AmpC enzymes are primarily involved in cell wall recycling they can hydrolyze many beta-lactam agents. Enterobacter cloacae complex, Klebsiella aerogenes, and Citrobacter freundii are most at risk for inducing AmpC production. IDSA Guidance document suggests that resistance to common beta-lactams (e.g., ceftriaxone, piperacillin-tazobactam) develops in 20% of infections caused by these agents.³ Carbapenem Resistant Enterobacterales (CRE) are another significant MDRO which can be caused by carabapenemases (CP-CRE; e.g., KPC, NDM, OXA-48, VIM, and IMP) or can be caused by non-enzyme mechanisms such as altered membrane porins and overproduction of AmpC or ESBL enzymes (CRE).^3,6

The IDSA recommends the following treatments when an ESBL, AmpC, CRE, and CP-CRE are identified below. Note dosing will be provided with the first instance and can be assumed to be the same throughout unless otherwise stated.

Uncomplicated cystitis caused by ESBL, AmpC, CRE, CP-CRE: ^3,7,8

First line recommendations:

• Oral nitrofurantoin (< 12 years: 1.25 – 1.75 mg/kg/dose 4 times a day; max 100mg/dose; ≥12 years: Macrobid 100 mg twice daily) or
• Oral sulfamethoxazole/trimethoprim (3 to 6 mg/kg/dose (trimethoprim component) PO twice daily; max 320 mg/dose).

Alternatives: all oral: ciprofloxacin (15mg/kg/dose twice daily; max 500mg/dose), levofloxacin (< 50 kg: 8 mg/kg/dose twice daily; max 500 mg/day, ≥ 50 kg: 500 mg once daily), or carbapenems.

Complicated urinary tract infections (e.g., pyelonephritis) caused by ESBL, AmpC, CRE, CP-CRE: ^3,5,9-12

First-line recommendations:

• For AmpC, ESBL, or CRE/CP-CRE: Sulfamethoxazole/trimethoprim or fluroquinolones are considered first line if susceptible.
• For CRE/CP-CRE: ceftazidime-avibactam (50 mg/kg/dose Q8h over 3 hours; max 2g/dose), meropenem-vaborbactam (40 mg/kg/dose Q8h over 3 hours; max 2 g/dose), imipenem-cilastain-relebactam (25 mg/kg/dose Q6h; max 1 g/dose), or cefiderocol (60 mg/kg/dose Q8h over 3 hours; max 2g/dose) are other first-line options.

Alternatives:

• For AmpC, ESBL, or CRE/CP-CRE: aminoglycoside (e.g., gentamicin – dosing depending on patient age)
• For ESBLs: carbapenems [e.g., meropenem (20mg/kg/dose q8h; max 2,000 mg/dose) or ertapenem (<13 years: 15mg/kg/dose q12h, max 1000 mg/day; ≥13 years: 1000 mg/day once daily)]

 For all other systemic infections caused by AmpC, ESBL, or CRE/CP-CRE:³

First-line recommendations: ^3,9,11

• AmpC: Cefepime dosing dependent on MIC, fully susceptible (i.e., MICs < 2 mg/L) 50 mg/kg/dose Q12h as 3-hour infusion or 50 mg/kg/dose Q8h as traditional 0.5 hour infusion can be used. For those with susceptible dose dependent organisms (e.g., MIC 4-8 mg/L) the 50 mg/kg/dose Q8h as a 3-hour infusion may be needed.
• ESBL and some CRE: Carbapenems, are recommended first-line for ESBL until the patient is well enough to transition to oral therapy (ertapenem is cautioned in critically ill or malnourished). In cases of CRE when only ertapenem is resistant, meropenem is susceptible (i.e., MIC < 1 mg/L) meropenem can be used at high dose-prolonged infusion (e.g., 40 mg/kg/dose Q8h over 3 hours).
• AmpC and ESBL(improving): Guidance suggests considering either sulfamethoxazole/ trimethoprim or fluoroquinolone, when the patient is well enough to transition to oral therapy and it is susceptible to the agent.
• CRE/CP-CRE: Patients with organisms that demonstrate resistance to carbapenems beyond ertapenem are recommended to receive ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-cilastain-relebactam.

Carbapenem-resistant Acinetobacter baumannii (CRAB)

Acinetobacter baumannii (A. Baumannii) is a major pathogen of significance that has demonstrated mortality rates in adults between 26-56%. ¹³  Firstline treatment recommendations include sulbactam-durlobactam with either imipenem-cilastin or meropenem. Limited data exists on sulbactam-durlobactam in pediatrics.  Based upon extrapolation and a population-pharmacokinetic model study, estimates suggest dose of 50 mg/kg/dose sulbactam Q6h (max 1g of each component/dose) and infused over 3-4 hours may be reasonable in cases of life-threatening A. baumannii infection.^3,14.

Difficult-to-Treat Resistant (DTR) Pseudomonas aeruginosa

Difficult to treat P. aeruginosa is defined by non-susceptibility to at least one antibiotic in three classes commonly active against P. aeruginosa. Preferred treatments include high-dose extended infusion of non-carbapenem beta-lactams for susceptible strains. For resistant strains, ceftolozane-tazobactam (30mg/kg q8h; max 1.5g/dose), ceftazidime-avibactam, or imipenem-cilastin-relebactam may be necessary.³

Stenotrophomonas maltophilia

Stenotrophomonas maltophilia (S. maltophilia) is a glucose non-fermenting gram-negative bacillus that produces metallo-beta-lactamases leading to resistance of many antibiotics. Decisions to provide targeted therapy for S. maltophilia are difficult as it is can sometimes be a colonizer and frequently identified within polymicrobial infections. Further, data comparing the effectiveness of commonly used agents for S. maltophilia are lacking. IDSA guidance recommended treatment includes any two of the following options: cefiderocol, sulfamethoxazole/ trimethoprim, levofloxacin, ceftazidime-avibactam in combination with aztreonam (30 mg/kg/dose 4 times daily; max 2000 mg/day) another one of the options would be minocycline (2 mg/kg/dose twice daily; max 100mg/dose – see pediatric considerations below).

Pediatric Specific Considerations:

In addition to dosing, there are other important considerations that should be considered when using antibiotics for pediatric patients with MDROs.

• Sulfamethoxazole/ trimethoprim is not generally recommended in children < 2 months; however it has been used in neonates in rare cases when the benefits outweigh the risks.^15-18
• Fluoroquinolones should only be used in pediatric patients when there is no other alternative or the only other option is parenteral therapy, this is because of significant adverse effects including tendinitis and tendon rupture, peripheral neuropathy, and central nervous system effects (e.g., dizziness, restlessness, confusion, and insomnia to toxic psychosis).^{19-21 .}
• Minocycline as a traditional tetracycline, is generally not recommended in pediatric patients less than 8 years of age due to teeth staining^8.

 

Table 1.  Summary of Treatment Recommendations

Resistant Organism	Preferred Therapy
Systemic Infection Caused by ESBL-producing Enterobacterales	Carbapenem
Systemic Infection Caused by AmpC-producing Enterobacterales	Cefepime, when able to transition to oral: sulfamethoxazole/trimethoprim or fluoroquinolone
CRE	If non CP-CRE, and only resistant to ertapenem: high dose extended infusion meropenem. CP-CRE: ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-cilastain-relebactam
DTR Pseudomonas aeruginosa	Ceftolozane-tazobactam, ceftazidime-avibactam, or imipenem-cilastin-relebactam
CRAB (Acinetobacter baumannii)	Sulbactam-durlobactam + carbapenem (imipenem-cilastin or meropenem)
Stenotrophomonas maltophilia	Any 2 of the Following: cefiderocol, sulfamethoxazole/ trimethoprim, levofloxacin, minocycline, or ceftazidime-avibactam plus aztreonam

 

About the author: Marissa Galicia 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. Centers for Disease Control and Prevention. Antimicrobial Resistant Threats in the United States 2021-2022. Accessed July 9, 2025https://www.cdc.gov/antimicrobial-resistance/data-research/threats/update-2022.html#:~:text=Findings,-resistant%20(MDR)%20Pseudomonas%20aeruginosa
2. Markham JL, Hall M, Burns A, et al. Antibiotic susceptibility patterns in US children’s hospitals. J Hosp Med. 2025
3. Tamma PD, Heil EL, Justo JA, et al. Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin Infect Dis. 2024
4. Batchelor HK, Marriott JF. Paediatric pharmacokinetics: key considerations. Br J Clin Pharmacol. 2015;79(3):395–404
5. Lockowitz CR, Hsu AJ, Chiotos K, et al. Suggested Dosing of Select Beta-lactam Agents for the Treatment of Antimicrobial-Resistant Gram-Negative Infections in Children. J Pediatric Infect Dis Soc. 2025;14(2):piaf004
6. Suay-García B, Pérez-Gracia MT. Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections. Antibiotics (Basel). 2019;8(3):122. doi: 10.3390/antibiotics8030122
7. Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management, Roberts KB. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128(3):595–610
8. Kimberlin DW, Banerjee R, Barnett E, Lynfield R, Sawyer MH. Red book: 2024-2027 Report of the Committee on Infectious Diseases American Academy of Pediatrics. Thirty-third edition. ed. American Academy of Pediatrics. Committee on Infectious Diseases, author.; American Academy of Pediatrics; 2024
9. Clinical and Laboratory Standards Institute. M100-ED35:2025 Performance Standards for Antimicrobial Susceptibility Testing. 35th ed. ; 2025
10. Ertapenem Product Information. Accessed Dec 3, 2025 https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021337s051lbl.pdf
11. Courter JD, Kuti JL, Girotto JE, Nicolau DP. Optimizing bactericidal exposure for beta-lactams using prolonged and continuous infusions in the pediatric population. Pediatr Blood Cancer. 2009;53(3):379–385
12. Bradley JS, Orchiston E, Portsmouth S, et al. Pharmacokinetics, Safety and Tolerability of Single-dose or Multiple-dose Cefiderocol in Hospitalized Pediatric Patients Three Months to Less Than Eighteen Years Old With Infections Treated With Standard-of-care Antibiotics in the PEDI-CEFI Phase 2 Study. Pediatr Infect Dis J. 2025;44(2). https://journals.lww.com/pidj/fulltext/2025/02000/pharmacokinetics,_safety_and_tolerability_of.9.aspx
13. Appaneal HJ, Lopes VV, LaPlante KL, Caffrey AR. Treatment, Clinical Outcomes, and Predictors of Mortality among a National Cohort of Admitted Patients with Acinetobacter baumannii Infection. 2022;66(3):1975
14. Onita T, Sano Y, Ikawa K, et al. Population Pharmacokinetic Analysis and Pharmacodynamic Evaluation of Sulbactam in Pediatric Patients: Dosing Suggestions for Acinetobacter baumannii Infections. J Pediatric Infect Dis Soc. 2025;14(5):piaf043. doi: 10.1093/jpids/piaf043
15. Ryan KL, Dersch-Mills D, Clark D. Trimethoprim-Sulfamethoxazole for Treatment of Stenotrophomonas maltophilia Pneumonia in a Neonate. Can J Hosp Pharm. 2013;66(6):384–387
16. Bang AT, Reddy HM, Deshmukh MD, et al. Neonatal and infant mortality in the ten years (1993 to 2003) of the Gadchiroli field trial: effect of home-based neonatal care. J Perinatol. 2005;25 Suppl 1:92
17. Bang AT, Bang RA, Baitule SB, et al. Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India. Lancet. 1999;354(9194):1955–1961
18. Bhutta ZA, Zaidi AKM, Thaver D, et al. Management of newborn infections in primary care settings: a review of the evidence and implications for policy? Pediatr Infect Dis J. 2009;28(1 Suppl):22
19. Jackson MA, Schutze GE, COMMITTEE ON INFECTIOUS DISEASES. The Use of Systemic and Topical Fluoroquinolones. Pediatrics. 2016;138(5):e20162706
20. Muradian M, Khan S. Levofloxacin-induced Psychosis in a Young Healthy Patient. Cureus. 2019;11(11):e6217
21. Tandan M, Cormican M, Vellinga A. Adverse events of fluoroquinolones vs. other antimicrobials prescribed in primary care: A systematic review and meta-analysis of randomized controlled trials. Int J Antimicrob Agents. 2018;52(5):529–540

 

By Sydney E. Kolosky, PharmD candidate

Neonatal late-onset sepsis is a systemic infection that is acquired from the hospital environment after 72 hours of life.¹ It represents a major cause of morbidity and mortality among neonates, particularly those born very preterm, with an incidence of 9% which results in approximately 11% lower risk of survival.² Unfortunately, despite improved infection prevention efforts, this decreased survival rate across all gestational ages remains.² The increase in mortality among the most preterm infants is, at least in part, one driver of antimicrobial usage in this population. Currently, there is an absence of specific recommendations guiding empirical antibiotic selection for treatment of late-onset sepsis in neonates due to variability in pathogens and local susceptibility.

The study Late Antibiotic Use Among Preterm Infants Admitted to the Neonatal Intensive Care Unit, published in 2025 by Coggins and colleagues, touches upon the impact of the variability for antibiotic selection in neonates with late-onset sepsis. It investigated antibiotic use among 420,000 infants from 2009-2023 to describe contemporary antibiotic patterns in preterm infants with late-onset neonatal sepsis.³ The study found that the use of antibiotics for late-onset sepsis was inversely proportional to the gestational age group with antibiotics being administered to 75% of infants born 22 to 24 week’s gestational age compared to about 4% of infants born 33 to 34 week’s gestational age.³ The Coggins study inspired this review, which will summarize the current United States epidemiology, causative pathogens, and antibiotic use trends to improve understanding and treatment of late-onset sepsis in neonates.

Causative Pathogens

Two articles from 2022 offer updated evidence regarding current pathogens driving neonatal late-onset sepsis in the United States. In 2022, the study Late-Onset Sepsis Among Very Preterm Infants, by Flannery and colleagues using the Vermont Oxford Network data, identified Gram-positive bacteria as the predominant pathogens accounting for 63% of isolates (29% coagulase-negative staphylococci, 23% Staphylococcus aureus, 5% Enterococcus spp., 5% Group B Streptococcus)²  The two most common Gram-negative bacteria identified included Escherichia coli (12%) and Klebsiella spp. (8%).² The review article Updates in Late-Onset Sepsis: Risk Assessment, Therapy, and Outcomes also reported that neonatal late-onset sepsis is primarily driven by Gram-positive bacteria, with coagulase-negative staphylococci isolated in more than half of gram-positive bacteremia among preterm infants.⁴ Although these data capture a broader picture of common causative pathogens in NICUs throughout the United States. Variation in pathogen patterns and susceptibility data across different geographic regions still exists and should be considered when selecting appropriate empiric treatment.

New Insights on Antibiotic Utilization in Late-Onset Neonatal Sepsis

To identify possible opportunities for antimicrobial stewardship, the 2025 study by Coggins and colleagues described recent trends in antibiotic utilization for late onset sepsis in the United States. The study found vancomycin and gentamicin was the most common regimen, representing 19% of all courses of antibiotics given after the first 72 hours of life, followed by ampicillin plus gentamicin (12%) and cefazolin (8%).³ Alternative regimens that contained gram-negative agents beyond gentamicin include cefotaxime and vancomycin (4%), tobramycin and vancomycin (4%), cefepime and vancomycin (3%), piperacillin/tazobactam (2%), ceftazidime and vancomycin (2%), amikacin and vancomycin (2%), cefepime (1%), meropenem and vancomycin (1%).³ Susceptibility data varies across geographic regions leading to certain antibiotics being resistant in specific areas of the country while others are susceptible in other areas. Ultimately, this susceptibility plays a major role in the choice of antibiotics and leads to variations in antibiotic regimens for this disease state.

In addition to studying the trends across combination antibiotic regimens, the study also looked at the individual components of the regimens. Vancomycin was the most common individual component (45%) in the antibiotic regimens, however, the use of vancomycin-containing regimens remarkably declined from 58.8% of all courses in 2009 to 36.0% in 2023 (P < .001).³ The decline of vancomycin occurred at the same time there were increases of prescriptions for antistaphylococcal penicillins (i.e., nafcillin, oxacillin [7% to 18%, P < .001]), piperacillin/tazobactam (3% to 9%, P < .001), and cefepime (2% to 12%, P < .001).³ Additionally, antibiotic choice notably changed over the course of NICU care with cefazolin becoming the main antibiotic exposed to the neonate after 90 days of age.³ The increased utilization of cefazolin suggests its use for surgical site infection prophylaxis in these older infants.

This study contributes new insights to late-onset neonatal sepsis in two important ways. First, it quantifies how antibiotic use in late-onset sepsis has shifted across the United States, illustrating changing stewardship priorities to reduce the use of broad-spectrum antibiotics in the neonatal population, particularly those with methicillin-resistant S. aureus (MRSA) coverage. Secondly, it demonstrates how significant variability exists in practice despite the availability of national guidance, underscoring the need for standardized empiric treatment frameworks that align with current microbiology, local resistance data, and American Academy of Pediatrics (AAP) recommendations.

Antibiotic Treatment Patterns in the United States

MRSA infections have been found to be less common in comparison to methicillin-susceptible S. aureus (MSSA) infections in late-onset sepsis.² In the neonatal population, S. aureus infections (either MRSA or MSSA) develop after the neonate is colonized with the bacteria. Colonization of MRSA in the NICU has been a focus of infection prevention and control initiatives, particularly those aimed at developing strategies and recommendations to de-colonize infants to prevent infection. The Centers for Disease Control and Prevention (CDC) and Society for Healthcare Epidemiology of America (SHEA) advocate for routine active surveillance of S. aureus, including MSSA and MRSA, especially in neonates with low birth weight who are at higher risk for infection.⁵ This strategy allows NICUs to determine the baseline S. aureus colonization status of a neonate. If a neonate is determined to be colonized with either MSSA or MRSA, SHEA suggests that intranasal mupirocin twice daily for 5-7 days for decolonization in the NICU population.⁵

The empiric treatment for late-onset sepsis can be tailored to the neonate based on their baseline S. aureus colonization status. The 2022 study Safety and Efficacy of Nafcillin for Empiric Therapy of Late-Onset Sepsis in the NICU by Nationwide Children’s Hospital concluded nafcillin is a safe alternative to vancomycin for empiric therapy in neonates with late-onset sepsis not colonized by MRSA as there was no difference in mortality.⁶ This is despite many infections being caused by coagulase-negative staphylococcus. It is also consistent with the AAP Red Book recommendation for MSSA infections, where nafcillin or oxacillin are recommended as preferred agents, especially when there is a risk for meningitis as cefazolin may not have optimal cerebrospinal fluid concentrations.⁷ For sepsis caused by MRSA, vancomycin remains the preferred agent.⁷

Gram-negative infections are less common than Gram-positive infections, accounting for roughly a quarter of neonatal late-onset sepsis infections.² The prevalence of these infections underscores the need for effective antimicrobial therapy targeting key Gram-negative pathogens, such as Escherichia coli and Klebsiella spp. For neonatal sepsis with suspected or confirmed infection by Enterobacterales or Group B Streptococci, the AAP Red Book recommends that ampicillin and an aminoglycoside be considered as first-line therapy.^8-10 Typically, gentamicin is the aminoglycoside of choice for neonates who have infections without central nervous system involvement.¹⁰

The 2023 study Antibiotic Use Among Infants Admitted to Neonatal Intensive Care Units, by Flannery and colleagues, concluded that gentamicin follows vancomycin as the second most prevalent empiric antimicrobial agent at 48% compared to 51%, respectively.¹¹ However, new data suggests that resistance to gentamicin is increasing with 7% of E. coli neonatal late-onset sepsis cases being gentamicin resistant.¹² If resistance precludes use of gentamicin, the AAP Red Book recommends replacement with ceftazidime, cefepime, amikacin, or a carbapenem.^9,10 The role of pharmacists is critical in this context to ensure individual institutions choose empiric therapy options that both cover isolates seen in their units and penetrate effectively to the source of infection, while also utilizing traditional stewardship efforts to guide clinicians towards the narrowest agents expected to cover the organisms of concern.

The duration of treatment is of equal importance to the selection of the empiric therapy itself and is another area of opportunity for antimicrobial stewardship. Although there are not any consensus guidelines in the United States, the National Institute for Health and Care Excellence (NICE) in the United Kingdom recommends an antibiotic treatment duration of 7 days in neonates with late-onset sepsis who have a positive blood culture, keeping in mind that causative organisms and source may also influence the duration.¹³ Additionally, NICE recommends that antibiotics be discontinued before 48 hours if the neonate has a negative blood culture and thought to no longer have an infectious cause.¹³ Recent data from Speier and colleagues found that the median antibiotic treatment durations for late-onset sepsis was 4 days for a culture-negative evaluation and 12 days for a culture-positive episode.¹⁴ The longer duration of treatment in both groups emphasizes the need for Antimicrobial Stewardship Program (ASP) targets to help ensure prompt discontinuation of antibiotics when treatment is no longer required to minimize antibiotic exposure and resistance development.

Conclusion

Neonatal late-onset sepsis remains a strong area of focus for ASP focus given the increased morbidity, mortality, and antibiotic exposure among neonates. While there is commonality in the antibiotics used to treat this condition based on predominant pathogens, treatment patterns still vary widely across the country. Recent shifts in antibiotic utilization reflect progress towards more targeted therapy informed by causative pathogens, local susceptibility data, and resistance trends, making this an important area for continued stewardship intervention. These findings also highlight the critical role pharmacists can play in guiding empiric antibiotic selection that incorporates local susceptibility data and assists in discussions regarding duration to limit excessive antibiotic exposure. Overall, continued efforts to standardize treatment practices and minimize unnecessary antibiotic exposure in the neonatal population are essential to improving ASP in this disease state.

 

Empiric Treatment Considerations*
No History of MRSA Colonization or Infection	nafcillin or oxacillin PLUS gentamicin, an extended-spectrum cephalosporin (e.g., ceftazidime, cefepime), amikacin, or a carbapenem
MRSA Colonization and/or History of MRSA Infection	vancomycin PLUS gentamicin, an extended-spectrum cephalosporin (e.g., ceftazidime, cefepime), amikacin, or a carbapenem

*Consider local susceptibility data when developing initial empiric antibiotic therapy plans.

 

About the author: Sydney E. Kolosky 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. Glaser MA, Hughes LM, Jnah A, Newberry D. Neonatal sepsis: A review of pathophysiology and current management strategies. Adv Neonatal Care. 2021;21(1):49–60. doi: 10.1097/ANC.0000000000000769.
2. Flannery DD, Edwards EM, Coggins SA, Horbar JD, Puopolo KM. Late-onset sepsis among very preterm infants. Pediatrics. 2022;150(6):e2022058813. doi: 10.1542/peds.2022–058813. doi: 10.1542/peds.2022-058813.
3. Coggins SA, Zevallos Barboza A, Puopolo KM, Flannery DD. Late antibiotic use among preterm infants admitted to the neonatal intensive care unit. Pediatrics. 2025;156(5):e2025071372. doi: 10.1542/peds.2025–071372. doi: 10.1542/peds.2025-071372.
4. Coggins SA, Glaser K. Updates in late-onset sepsis: Risk assessment, therapy, and outcomes. Neoreviews. 2022;23(11):738–755. doi: 10.1542/neo.23-10-e738.
5. Akinboyo IC, Zangwill KM, Berg WM, Cantey JB, Huizinga B, Milstone AM. SHEA neonatal intensive care unit (NICU) white paper series: Practical approaches to staphylococcus aureus disease prevention. Infect Control Hosp Epidemiol. 2020;41(11):1251–1257. doi: 10.1017/ice.2020.51.
6. Magers J, Prusakov P, Speaks S, Conroy S, Sánchez PJ. Safety and efficacy of nafcillin for empiric therapy of late-onset sepsis in the NICU. Pediatrics. 2022;149(5):e2021052360. doi: 10.1542/peds.2021–052360. doi: 10.1542/peds.2021-052360.
7. Staphylococcus aureusCommittee 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-S3_018_008. 10.1542/9781610027373-S3_018_008.
8. Puopolo KM, Lynfield R, Cummings JJ, et al. Management of infants at risk for group B streptococcal disease. Pediatrics. 2019;144(2):e20191881. https://doi.org/10.1542/peds.2019-1881. Accessed 11/14/2025. doi: 10.1542/peds.2019-1881.
9. Group B streptococcal infectionsCommittee 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-S3_018_011. Accessed 11/14/2025. 10.1542/9781610027373-S3_018_011.
10. Serious neonatal bacterial infections caused by enterobacterales (including septicemia and meningitis)Committee 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-S3_005_002. Accessed 11/20/2025. 10.1542/9781610027373-S3_005_002.
11. Flannery DD, Zevallos Barboza A, Mukhopadhyay S, et al. Antibiotic use among infants admitted to neonatal intensive care units. JAMA Pediatr. 2023;177(12):1354–1356. https://doi.org/10.1001/jamapediatrics.2023.3664. Accessed 11/14/2025. doi: 10.1001/jamapediatrics.2023.3664.
12. Hoffman A, Satyavolu S, Muhanna D, et al. Predictors of mortality and severe illness from escherichia coli sepsis in neonates. J Perinatol. 2024;44(12):1816–1821. doi: 10.1038/s41372-024-02117-9.
13. National Institute for Health and Care Excellence (NICE). Neonatal infection: Antibiotics for prevention and treatment. 2024.
14. Speier RL, Cotten CM, Benjamin DKJ, et al. Late-onset sepsis evaluation and empiric therapy in extremely low gestational age newborns. J Pediatric Infect Dis Soc. 2023;12(Supplement_2):S37–S43. doi: 10.1093/jpids/piad068.

It is Antibiotic Awareness week! It is a great time to renew our understandings and efforts regarding appropriate use of antibiotics, as inappropriate usage can lead to unnecessary resistance and adverse effects.  For 2025, the CDC’s theme is “Fighting Antimicrobial Resistance Takes All of Us”.

There are two easy ways we as pharmacists can help improve antibiotic usage for our youngest patients. 

• ️The first is to recommend/provide immunizations to help prevent the children from getting significant illnesses.
  1. Recommend/provide routine and seasonal childhood immunizations.
  2. In the fall, provide additional education to parents regarding seasonal immunizations that are appropriate for the infant/child’s age (e.g., RSV mab, influenza vaccine, COVID-vaccine)
• ‍‍Educate parents about what infections are most likely caused by viruses versus bacteria. When the kids are sick, it is good to explain to the parents that the best care for respiratory viruses (other than flu and COVID-19) is supportive management. The CDC has a nice summary here.  This often includes hydration and targeted symptom management with things such as antipyretics, honey (if > 12 months), and nasal saline.  It is important to educate parents that antibiotics will not help treat viral infections.  Explaining that by not using the antibiotics when they will not help, they will help save the antibiotics for the conditions when they are needed (e.g., group A streptococcal pharyngitis, otitis media in some cases).

 

As mentioned above, Flu and COVID-19 are two viral conditions that have specific treatments.  These treatments are reserved for those with severe disease or at high risk for severe disease.  For flu this includes all children who are less than 2-5 years old with oseltamivir.  While COVID-19 treatment recommendations are provided by the Infectious Diseases Society of America.

 

For more resources Go Purple and visit the USAAW Resources: https://www.cdc.gov/antimicrobial-resistance/communication-resources/usaaw.html

 

A recent article by Kaplan and colleagues was published in the Journal of Pediatric Infectious Diseases in November 2025 evaluating the pneumococcal serotypes and susceptibility of invasive pneumococcal disease in children.¹ In this article, the authors evaluated pediatric pneumococcal disease in children admitted to 8 hospitals across the United States from 2018 – 2023. These findings help us identify information on which pneumococcal diseases continue to occur despite vaccination, inform current empiric treatment strategies in children and help identify areas for targeted stewardship interventions.

Pneumococcal Disease and Conjugate Vaccine History

To fully understand this article, it is essential to understand the history of the pneumococcal disease and vaccination. Pneumococcal disease has significantly cased invasive infections in young and old as well as those with significant chronic conditions including immunocompromise. The incidence of these infections has been greatly reduced from ~ 25 per 100,000 in late 1990’s to < 10 per 100,000 in 2023.² This reduction has been primarily due to pneumococcal vaccination. In 2010, the pneumococcal conjugate 13 valent vaccine (PCV13) replaced the 7 valent vaccine (PCV7). A key advantage of this broadening was the coverage of serotype 19A, which was a major cause of severe, antibiotic resistant infections in young children.³ More recently, the 15 and 20 valent pneumococcal vaccines (PCV15, PCV20) were recommended for use in children in 2022 and 2023, respectively.^4-7

Study Key Findings

Despite overall numbers of invasive pneumococcal disease decreasing, breakthrough infections (e.g., those caused by PCV13 strains), do occur.  This study found that 30% of the cases were caused by PCV13 strains, particularly pneumonia and mastoiditis.¹. In contrast, infections such as bacteremia, meningitis, peritonitis, and bone and joint infections were more commonly caused by strains not covered by the PCV13 vaccine.¹ It is estimated that up to 23% of the isolates with non-PCV13 strains may be covered by the newer vaccines.¹

Fortunately, non-CNS isolates were reported to have low non-susceptibility rates to both penicillin (4%) and ceftriaxone (3%).  Of those that were resistant, they continued to be primarily caused by serotype 19A.  Concerningly, meningitis isolates that were tested using CNS breakpoints demonstrated higher rates of non-susceptibility with about 40% non-susceptible to penicillin and 10% to ceftriaxone (majority were serotypes 19A and 35B).¹  This suggests there is continued need to use combination empiric therapy for meningitis in children.

Pharmacist Considerations

For pharmacists, these findings reinforce empiric therapy recommendations.  Amoxicillin (or IV ampicillin) remains appropriate for most invasive pneumococcal infections in children (e.g., pneumonia).  Unfortunately, neither penicillin nor ceftriaxone should be relied upon alone for empiric pneumococcal meningitis treatment, instead vancomycin still should be combined with ceftriaxone.

As broader spectrum PCVs (i.e., PCV15, PCV20) are now commonly used, ongoing surveillance for pneumococcal serotypes and resistances will be important to guide future antibiotic treatment recommendations.

 

References

1. Kaplan SL, Barson WJ, Ling Lin P, et al. Invasive Pneumococcal Disease at Eight Children’s Hospitals in the United States, 2018-2023. Pediatr Infect Dis J. 2025. doi: 10.1097/INF.0000000000005039. Epub 2025 Nov 7.
2. Centers for Disease Control and Prevention. Pneumococcal Disease Surveillance and Trends. Accessed November 11, 2025 https://www.cdc.gov/pneumococcal/php/surveillance/index.html
3. Centers for Disease Control and Prevention (CDC). Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children – Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep. 2010;59(9):258–261
4. Kobayashi M, Farrar JL, Gierke R, et al. Use of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization Practices – United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(37):1174–1181
5. American Academy of Family Physicians. Immunization Schedules. Accessed November 13, 2025https://www.aafp.org/family-physician/patient-care/prevention-wellness/immunizations-vaccines/immunization-schedules.html
6. American Academy of Pediatrics, Committee on Infectious Diseases. Red Book : Report of the Committee on Infectious Diseases 2024 – 2027. AAP Immunization Schedule. Accessed November 14, 2025https://publications.aap.org/redbook/resources/15585
7. ACIP Updates: Recommendations for Use of 20-Valent Pneumococcal Conjugate Vaccine in Children – United States, 2023MMWR Morb Mortal Wkly Rep. 2023;72(39):1072

The Essential Role of Pharmacists in Pediatric COVID-19 Vaccination

Evidence shows that pharmacists played a key role in COVID-19 vaccines for patients of all ages, including children, during the peak of the pandemic. Specifically, in the first three years of the pandemic (12/2020 – 9/2023) pharmacists provided 13 – 57% of all pediatric COVID-19 vaccines.¹ Although most children receive most of their vaccines at their doctor’s office, survey data suggests about 15% (especially teens and those in cities) obtain routine vaccines from pharmacies.² The pharmacist is the most accessible healthcare provider, with 89% of American’s living within 5 miles of a pharmacy.³ Thus, pharmacies remain an essential access point for vaccines for children.

Making Sense of COVID-19 Vaccine Recommendations for Kids

In recent months, the rules for when one can and should recommend COVID-19 vaccines to children has become confusing. The Advisory Committee on Immunization Practices has voted and Centers for Disease Control and Prevention (CDC) have changed COVID-19 vaccine for those 6 months and older to a shared clinical decision recommendation.⁴ It is important that it remains recommended at least at this level, as this will allow it to be paid for by the VFC program.

Meanwhile, the American Academy of Pediatrics (AAP) has made a stronger statement clearly recommending the COVID-19 vaccine for all infants and children 6 months through 23 months of age, as well as those 2 through 18 years old who: are unvaccinated, are at high risk of severe COVID-19 disease, live in congregate settings, have household members at high risk of severe COVID-19 disease, or whose parent/guardian wishes to provide them with additional protection.⁵

It is important to note, although confusing, these vaccine recommendations are not in conflict but rather differ in emphasis. The AAP guidance more clearly states which children are at highest risk and should be recommended to receive the vaccine while the CDC allows for individual decision-making. Notably, the CDC report shows that children < 2 years of age are at one of the highest risks of being hospitalized from COVID-19 disease, second only to those > 75 years old.⁶ As such, it is clear why this age is a routine recommendation, per the AAP. The AAP provides clear evidence for each of their recommendations in their COVID-19 specific recommendations.⁷

Which Pediatric Patients are Pharmacists Authorized to Vaccinate Against COVID-19 in 2025-26?

Which of our pediatric patients can we as pharmacists provide the COVID-19 vaccine to?  That partially depends on which state one is practicing.  The 12^th PREP Act extension allows pharmacists in every state to continue to provide COVID-19 and flu vaccines down to 3 years of age, in accordance with ACIP/CDC recommendations.⁸  Beyond this federal authorization, vaccine administration regulations revert to each state’s law.  We published an updated chart with links in a recent JPPT article to help clarify these requirements and provide you with quick access to state-specifics.⁹

References

1. El Kalach R, Jones-Jack NH, Grabenstein JD, et al. Pharmacists’ answer to the COVID-19 pandemic: Contribution of the Federal Retail Pharmacy Program to COVID-19 vaccination across sociodemographic characteristics-United States. J Am Pharm Assoc (2003). 2025;65(1):102305
2. Kang Y, Zhang F, Vogt TM. Where do children get vaccinated in the U.S.? Parental experiences, attitudes, and beliefs about place of vaccination with a focus on pharmacies and schools. 2025;62:126801
3. Berenbrok LA, Tang S, Gabriel N, et al. Access to community pharmacies: A nationwide geographic information systems cross-sectional analysis. J Am Pharm Assoc (2003). 2022;62(6):1816–1822.e2
4. Centers for Disease Control and Prevention. Child and Adolescent Immunization Schedule by Age (Addendum updated August 7, 2025). Accessed September 20, 2025https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.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 September 20, 2025https://publications.aap.org/redbook/resources/15585
6. Centers of Disease and Prevention. Updates to COVID-19 epidemiology. 2025. https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/02-Srinivasan-covid-508.pdf
7. Committee on Infectious Diseases. Recommendations for COVID-19 Vaccines in Infants, Children, and Adolescents: Policy Statement. 2025
8. Health and Human Services Department. 12th Amendment to Declaration Under the Public Readiness and Emergency Preparedness Act for Medical Countermeasures Against COVID-19. 2024;89(238):99875–99883. https://www.federalregister.gov/documents/2024/12/11/2024-29108/12th-amendment-to-declaration-under-the-public-readiness-and-emergency-preparedness-act-for-medical#:~:text=The%20Public%20Readiness%20and%20Emergency%20Preparedness%20(PREP)%20Act%20authorizes%20the,relating%20to%2C%20or%20resulting%20from
9. Girotto JE, Warminski S, Oz T, Fly JH. Continuing as Partners in Immunization: Updates to Practice and Legislation for Pediatric Pharmacy Immunizations. J Pediatr Pharmacol Ther. 2025;30(5):691–695

 

 By Debonique Burton

Respiratory Syncytial Virus (RSV) is a very common respiratory virus that in most patients often presents with cold-like symptoms such as fever, sneezing, runny nose, cough, and/or decreased appetite.​ Unfortunately, in infants and those with risk factors for severe disease, can cause more serious illness such as bronchiolitis and pneumonia.  RSV has been the most common cause of hospital admissions among infants in the United States, leading to approximately 50,000 to 80,000 hospitalizations each year in children younger than five.​^1,2​  Data from the Respiratory Syncytial Virus (RSV) Hospitalization Surveillance Network (RSV-NET ~300 hospitals in 16 states) and the New Vaccine Surveillance Network (NVSN outpatient networks in 7 US sites), surveillance networks showed a significant reduction of RSV-related hospitalizations in children under 5 years old from 11,581 in 2018-2020 to 6,708 in 2024-2025.​³​  Specifically, this was a reduction of 28% based on NVSN data and 43% based on RSV-NET data after  the introduction of preventative RSV immunizations.​³ The authors also noted month by month reductions for those 0–7 months during the RSV immunization roll out, further evidence supporting that the change was most likely due to RSV immunizations.​³

 

Options to Protect Infants Against RSV

RSV immunizations were introduced in the fall of 2024 and included RSV vaccine RSVpreF (Abrysvo, the only RSV vaccine FDA-approved for pregnant patients) and infant monoclonal antibody nirsevimab (Beyfortus). More recently, clesrovimab (Enflonsia), another infant monoclonal antibody has become FDA approved and recommended as another option to protect infants against severe RSV lower respiratory.^4-6​

 

Impact of RSV Immunization in Infants

The 2024–2025 RSV season was the first in the U.S. with widespread use of both the maternal RSV vaccine and nirsevimab. Data from the National Immunization Survey showed that the percentage of U.S. infants aged 0–7 months protected by either approach (i.e., maternal vaccination or infant monoclonal antibody administration) rose from 30% in October 2024 to 66% by February 2025. This increase coincided with significant declines in RSV-related hospitalizations. The decrease was even more noticeable when excluding Houston, where prevention products were not widely available early in the season​.³​ The real-world drop in hospitalizations aligns with clinical trials which reported 80% efficacy of nirsevimab and about 70% efficacy of Abrysvo for preventing hospitalization among young infants.^2,7,8

Data from the phase 3 trial which included 901 infants up to 1 year of age, evaluated the safety, efficacy, and pharmacokinetics of clesrovimab in infants and children at increased risk for severe RSV disease reported that clesrovimab reduced the risk of RSV-related hospitalization for lower respiratory tract infection by about 91% compared to the control group [95%CI, 90.9 (76.2, 96.5)]​​.¹⁰  Clesrovimab was found to be well tolerated in infants considered at high risk for RSV. The most frequently reported side effects of clesrovimab included redness at the injection site (3.8%), swelling at the injection site (2.7%), and rash (2.3%)​​.^1,10

 

Recommendations for RSV Immunization

It is recommended that pregnant individuals between 32 and 36 weeks 6 days gestation, if not previously vaccinated against RSV, should receive RSVpreF vaccine September through January.^6,9  In cases when the mother did not receive the RSVpreF or receive it less than 14 days prior to delivery their infants < 8 months old are recommended to either nirsevimab or clesrovimab monoclonal antibody between October and March either at discharge from the hospital or at the first available visit in this timepoint.^4,5,9   There are also some high-risk infants and young children (i.e., those 8-19 months old) with specific risk factors for severe RSV disease including those who have chronic lung disease of prematurity (and receiving steroids, diuretics, or oxygen within the past 6 months), severe immunocompromise, cystic fibrosis or are American Indian or Alaska Native.^4,5,9 These high-risk individuals should receive nirsevimab just prior to the beginning of their second RSV season.^4,5,9​  At this time, there is not currently a preference for one method over another.

 

Summary – Infant RSV Immunization Recommendations^4-6

Immunization Product	Recommendations	Dosing
Maternal Vaccination Abrysvo (RSVpreF)	Pregnant individuals who have not yet received any RSV vaccine should receive a single dose of Abrysvo (RSVpreF) between 32 and 36 weeks, 6 days gestation, preferably from September through January in most areas of the U.S.	All: 0.5 mL IM
Infant Immunization with Monoclonal Antibody  Beyfortus (Nirsevimab) or Enflonsia (Clesrovimab)	Recommended from October through March (in most areas of the U.S.): • Infants <8 months whose mother did not receive RSVpreF ≥14 days before birth during this pregnancy should receive either nirsevimab or clesrovimab. • Children 8–19 months at higher risk for severe RSV should receive nirsevimab.	Nirsevimab: • <8 months: 50 mg or 100 mg IM (depending on weight) • 8–19 months: 200 mg IM Clesrovimab: • 105 mg IM

 

About the author: Debonique Burton 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. Maternal/Pediatric Work Group of the Advisory Committee on Immunization Practices. Evidence to Recommendation Framework: Clesrovimab. Accessed July 9, 2025. Available at: https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/05-MacNeil-Mat-Peds-RSV-508.pdf
2. Moline HL, Tannis A, Toepfer AP, et al. Early Estimate of Nirsevimab Effectiveness for Prevention of Respiratory Syncytial Virus-Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season – New Vaccine Surveillance Network, October 2023-February 2024. MMWR Morb Mortal Wkly Rep. 2024;73(9):209–214.
3. Patton ME, Moline HL, Whitaker M, et al. Interim Evaluation of Respiratory Syncytial Virus Hospitalization Rates Among Infants and Young Children After Introduction of Respiratory Syncytial Virus Prevention Products – United States, October 2024-February 2025. MMWR Morb Mortal Wkly Rep. 2025;74(16):273–281.
4. American Academy of Pediatrics, Committee on Infectious Diseases. Red Book: Report of the Committee on Infectious Diseases 2024 – 2027. Immunization Schedules. Accessed September 20, 2025. Available at: https://publications-aap-org.ezproxy.lib.uconn.edu/redbook/book/755/Red-Book-2024-2027-Report-of-the-Committee-on
5. Centers for Disease Control and Prevention. Child and Adolescent Immunization Schedule by Age (Addendum updated July 2, 2025). Accessed September 20, 2025. Available at: https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html
6. Centers for Disease Control and Prevention. Adult Immunization Schedule by Age (Addendum updated July 2, 2025). Accessed September 20, 2025. Available at: https://www.cdc.gov/vaccines/hcp/imz-schedules/adult-age.html
7. Alandijany TA, Qashqari FS. Evaluating the efficacy, safety, and immunogenicity of FDA-approved RSV vaccines: a systematic review of Arexvy, Abrysvo, and mResvia. Front Immunol. 2025;16:1624007.
8. Simões EAF, Pahud BA, Madhi SA, et al. Efficacy, Safety, and Immunogenicity of the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Respiratory Syncytial Virus Prefusion F Protein Vaccine Trial. Obstet Gynecol. 2025;145(2):157–167.
9. American Academy of Pediatrics, Committee on Infectious Diseases. AAP Recommendations for the Prevention of RSV Disease in Infants and Children. In: AAP Recommendations for the Prevention of RSV Disease in Infants and Children Red Book : Report of the Committee on Infectious Diseases 2024 – 2027.
10. Heather J Zar &, Louis J Bont, Paolo Manzoni M, et al. Phase 3, Randomized, Controlled Trial Evaluating Safety, Efficacy, and Pharmacokinetics (PK) of Clesrovimab in Infants and Children at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease. 2025;Volume 12 (supplement 1).

 

By Caroline Frost, PharmD candidate

Urinary tract infections (UTIs) are a common childhood infection. About 90% of pediatric UTIs occur in females.​¹​ Uropathogenic Escherichia coli accounts for about 80% of UTIs in children, specifically 83% in females and 50% in males. Other uropathogens include Enterococcus species (5% females, 17% males), Proteus mirabilis (4% females, 11% males), and Klebsiella sp (4% females, 10% males).​² Uropathogen invasion can lead to kidney inflammation and scarring as well as impaired kidney function.​³​

Urine cultures alone cannot be used to diagnose a UTI, UTICalc is a validated calculator developed to incorporate symptoms and risk factors in those 2-23 months of age to determine if testing is needed and if so if it is best to begin empiric therapy.⁴ A UTI with fever suggests a systemic infection, potentially pyelonephritis, which could result in kidney injury.​³​ Those with febrile UTI should usually be treated right away to prevent kidney injury from occurring.​³​

The American Academy of Pediatrics (AAP) retired their last iteration of their guidelines for infant UTIs (i.e., ages 2 to 24 months) in May 2021 and there have not been national guidelines for those 2 – 12 years.​⁵​  The recommended duration of antibiotic therapy in the retired AAP guidelines suggested 7 to 14 days (with no preference between them as data comparing 7,10, and 14 days were limited), with 7 days as the minimum due to 1 to 3 day durations shown to be inferior.​⁵​ The AAP’s general infectious diseases recommendations in the 2024 Redbook recommends 5-10 days for outpatient UTI treatment, 7-10 days for inpatient UTI treatment, and for those adolescents with simple cystitis only 3-5 days duration.​⁶​

Where did these shorter durations come from? 

New data have been published on the duration of antibiotic treatment for pediatric UTIs in recent years. A retrospective cohort analysis published in January of 2020 evaluated the association of antibiotic treatment duration with recurrence of uncomplicated UTI in pediatric patients.​⁷​ This study utilized data from a claims database from 2013-2015 and included 7,698 pediatric patients 2 to 17 years old diagnosed with acute cystitis or acute pyelonephritis in an ambulatory setting that filled a prescription for either amoxicillin with or without clavulanate, ampicillin, a cephalosporin (any), trimethoprim-sulfamethoxazole, ciprofloxacin, levofloxacin, or nitrofurantoin with a 7, 10, or 14 day supply.​⁷​ Prescriptions for a 3 to 5 day supply were only included if they were for a diagnosis cystitis.​⁷​ Authors reported that no difference was seen in recurrence/reinfection rates when comparing 7 days to 10 days and comparing 7 days to 14 days were compared (compared to 7 days: 10 days, OR 1.07, 95% CI 0.85-1.33; 14 days, OR 0.89, 95% CI 0.45-1.78).​⁷​ These findings suggest a 7 day course of antibiotics is not associated with increased risk of relapse or reinfection in cases of pediatric cystitis and pyelonephritis.  It supports avoiding longer duration of antibiotic treatment in these patients 2 – 17 years old.

A meta-analysis published in December 2024 further evaluated short-course therapy compared with standard-course durations for children with UTI.​⁸​ The meta-analysis included 9 randomized controlled trials (n=1,171 pediatric patients < 18 years old) that evaluated efficacy of short-course (2-5 days) versus standard-course (6-14 days) treatment for acute UTI (including afebrile and febrile UTI) in children 2 months to 18 years of age.​⁸​ The authors reported that those randomized to short-course therapy had a 2.2% higher risk of treatment failure, but this difference was significant only for those who presented without fever (3.8% increased risk in this group).​⁸​ However, due to unexplained heterogeneity between studies and a small number of children across studies presenting with febrile UTI, the data are not clear enough to suggest short-course therapy in pediatric patients presenting with febrile UTI despite this outcome.​⁸​ This meta-analysis also reported no significant difference between treatment groups in UTI and bacteriuria 25-60 days after completing treatment.​⁸​ In summary, this study provides further evidence to support shorter durations of antibiotics for children with UTIs.  The SCOUT trial was a randomized clinical noninferiority trial published in June 2023 that included patients ages 2 months to 10 years old with symptomatic UTI.​⁹​ While this trial was included in the 2024 meta-analysis previously discussed, its focus on children 2 months to 10 years old makes it important to view the specific data in this very young but important age group.  Six hundred ninety-three children were included and randomized to either 10 or 4 days (plus 5 days placebo) therapy.​⁹​ Importantly, inclusion was determined at day 5 and only in those who showed signs of clinical improvement.​⁹​ Authors reported rates of treatment failure 0.6% 5 days vs 4.2% 10 days and recurrence within 9 days of study product discontinuation 2.7% 5 day vs 4.2% 10 day treatment groups.​⁹​ Although 5 days of therapy was statistically inferior to the standard 10 day durations, the authors noted those who were likely to fail had uncomplicated disease (e.g., UTI without fever) and unlikely to have their UTI associated with scarring ​⁹​. They calculated that the number of patients needed to treat to prevent one febrile UTI treatment failure was 67 and more importantly, quite a large number, 469 patients, exactly, would need to be treated to prevent one child from having kidney scaring.​⁹​ Looking at all of the information in context, the authors suggest that short-course antibiotics could be a reliable option for children 2 months – 10 years old with UTI with or without fever who demonstrate clinical improvement after 5 days of antibiotics.​⁹​ The evidence gathered from these three articles suggests that 5 to 7 day durations for antibiotics can be a consideration for the treatment of pediatric UTIs.

What other options can be considered?

There has also been discussion of single dose aminoglycoside therapy for UTIs. A 2018 systematic review evaluated single dose aminoglycoside therapy (i.e., netilmicin, gentamicin, amikacin) using 13 articles representing 13,804 patients, 53.8% of which were children.¹⁰​  Articles that studied pediatrics included ages 2 weeks to 16 years old (except one article that did not report age of participants).​¹⁰ Most of the pediatric specific studies included those with afebrile UTI. Microbiological cure was reported to be 84.5% +/- 4.3% with a 19.0% rate of 30 day recurrence.​¹⁰​ Only 2 studies included evaluated clinical cure, with clinical cure rates of 82.8% and 94.7%.​¹⁰​ This systematic review suggests that single dose aminoglycoside therapy may be reasonable for pediatric patients presenting with afebrile UTI.​¹⁰​ There was no recommendation for single dose aminoglycosides in the AAP 2011 guidelines at all, so this would be an extension to the guidelines if implemented. Single dose aminoglycoside therapy could be beneficial for patients who are not likely to be adherent to multiple days of outpatient oral medications. However, due to lack of robust data for pediatric patients, I think clinicians in most cases should wait for more data specific to pediatrics before implementing single dose aminoglycoside therapy for pediatric patients.

But What About WikiGuidelines?

In response to new evidence, A WikiGuidelines Group Consensus Statement was published in November 2024 and provided recommendations that included treatment of pediatric UTI.​¹¹​ Unfortunately, due to the limited amount of pediatric specific data they were unable to make a clear recommendation on duration of treatment in pediatric UTI.​¹¹​ It suggested that shorter courses, including an option for single dose aminoglycosides, may be comparable to longer courses and considered reasonable for afebrile UTI in children >2 months old with low likelihood of pyelonephritis.¹⁰ Regarding treatment of pyelonephritis, it is stated that available data is inadequate to provide any recommendation for children >2 months old, but data suggests similar clinical success with 5-9 days versus 10-14 days of treatment.​¹¹​

Summary

Overall, newer evidence suggests that shorter durations of antibiotic therapy is likely reasonable for pediatric afebrile UTI. The data for treatment duration in febrile UTI is less uncertain, the AAP Redbook recommend a range of 5 to 10 days for treatment of outpatients and 5 -10 days for treatment of inpatients, it is likely safe to lean towards the 7 days of therapy as opposed to 10 days or longer for those with fever. From the data gathered across these newer studies, 5 days of therapy is may be considered for afebrile UTI in pediatric patients that are clinically improving by day 5.

Antibiotic Durations for Pediatric UTIs: What’s Changing?

Guideline Recommendation	Recent Evidence	Potential Change
2011 AAP Guidelines (retired): (2 – 24 months) 7–14 days for cystitis and pyelonephritis   2024 Wikiguidelines: (> 2 months) limited data consider 3–5 days for cystitis; 5–9 days for pyelonephritis   2024 AAP Red Book: (not neonate) 5–10 days for outpatient UTIs; 7–10 days for inpatient UTIs; 3–5 days for simple cystitis in adolescents (longer if complicated)	2020 Retrospective cohort (ages 2–17 yrs): Duration not linked to relapse or recurrence (3–5 days for cystitis; 7 days for pyelonephritis)     2024 Meta-analysis (ages <18 yrs): Short-course (2–5 days) may be reasonable for afebrile UTIs	Consider 5 days for acute cystitis and 7 days for acute pyelonephritis in those 2 months and older.  (Additional durations may still be needed if not clinically improved or for complicated disease)

About the author: Caroline Frost 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. Sood A, Penna FJ, Eleswarapu S, et al. Incidence, admission rates, and economic burden of pediatric emergency department visits for urinary tract infection: Data from the nationwide emergency department sample, 2006 to 2011. J Pediatr Urol. 2015;11(5):246.e1–246.e8. 10.1016/j.jpurol.2014.10.005.

​2. Edlin RS, Shapiro DJ, Hersh AL, Copp HL. Antibiotic resistance patterns of outpatient pediatric urinary tract infections. J Urol. 2013;190(1):222–227. doi: 10.1016/j.juro.2013.01.069.

​3. Mobley HLT, Donnenberg MS, Hagan EC. Uropathogenic escherichia coli. EcoSal Plus. 2009;3(2):10.1128/ecosalplus.8.6.1.3. doi: 10.1128/ecosalplus.8.6.1.3. 

​4. Marsh MC, Junquera GY, Stonebrook E, Spencer JD, Watson JR. Urinary tract infections in children. Pediatr Rev. 2024;45(5):260–270. doi: 10.1542/pir.2023-006017. 

​5. Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management, Roberts KB. Urinary tract infection: Clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128(3):595–610. doi: 10.1542/peds.2011-1330. 

​6. 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 7/17/2025. 10.1542/9781610027373-TAB.

​7. Afolabi TM, Goodlet KJ, Fairman KA. Association of antibiotic treatment duration with recurrence of uncomplicated urinary tract infection in pediatric patients. Ann Pharmacother. 2020;54(8):757–766. doi: 10.1177/1060028019900650. 

​8. Mueller GD, Conway SJ, Gibeau A, Shaikh N. Short- versus standard-course antimicrobial therapy for children with urinary tract infection: A meta-analysis. Acta Paediatr. 2025;114(3):479–486. doi: 10.1111/apa.17546. 

​9. Zaoutis T, Shaikh N, Fisher BT, et al. Short-course therapy for urinary tract infections in children: The SCOUT randomized clinical trial. JAMA Pediatr. 2023;177(8):782–789. doi: 10.1001/jamapediatrics.2023.1979. 

​10. Goodlet KJ, Benhalima FZ, Nailor MD. A systematic review of single-dose aminoglycoside therapy for urinary tract infection: Is it time to resurrect an old strategy? Antimicrob Agents Chemother. 2018;63(1):e02165–18. Print 2019 Jan. doi: 10.1128/AAC.02165-18. 

​11. Nelson Z, Aslan AT, Beahm NP, et al. Guidelines for the prevention, diagnosis, and management of urinary tract infections in pediatrics and adults: A WikiGuidelines group consensus statement. JAMA Netw Open. 2024;7(11):e2444495. https://doi.org/10.1001/jamanetworkopen.2024.44495. Accessed 7/7/2025. doi: 10.1001/jamanetworkopen.2024.44495.

I have been a pharmacist that has been practicing for more than 20 years, and throughout this time, the US has alwways had an infant hepatitis B vaccine strategy in place.  But this has not always been the case.  Let’s look back in time to learn more.  The first hepatitis B vaccine was introduced into the US in 1982.  Initially, only those at high risk of hepatitis B disease were vaccinated, but cases remained high (10-13 per 100,000).  In 1991 hepatitis B vaccination was changed to universal infant immunization and high-risk adolescent to vaccine and rates finally started coming down.   This was followed in 1995 recommending routine catch-up vaccination for adolescents.  Most recently in 2022 routine adult catch-up vaccination through age 59 years. By 2023 the rate dropped to 0.7 per 100,000 population. Universal infant vaccination, not selective high risk hepatitis B vaccination is what reduced hepatitis B incidence in the US.

Why Infant Vaccination Matters

When babies and young children acquire Hepatitis B the risk of developing chronic infection is very high (90% of infants that acquire hepatitis B go on to having chronic disease). Among newborns that acquire hepatitis B about one in four will eventually die as a result of chronic liver disease.

It is estimated that about 2.4 million individuals in the US are living with hepatitis B, but only about half are aware of their status.  About 10% of children acquire hepatitis B through community or household exposures, which is known as their mother have tested negative.  This is possible because Hepatitis B is one of the most contagious and viable bloodborne pathogens. It can survive in the environment for up to 7 days, making indirect transmission possible.

For these reasons, it is critically important to protect newborns as early as possible through vaccination.

Who Should Get Vaccinated

• All infants at birth begin 3 dose hepatitis B series (95% protection)
  • Those who are born to hepatitis B infected mothers should get first hepatitis B vaccine dose and a dose of hepatitis B immune globulin within 12 hours (results in 94% protection)
• Catch-up of those who did not receive the protection through age 59 years
  • Pediatrics – 2 hepatitis B only products, primarily 3 dose series although 2 dose option is available for teens
    • Also included in multiple combination vaccines
  • Adults 3 products currently available 2 are 3 dose series, 1 is available with a 2 dose series.
    • Also included in one combination vaccine with hepatitis A

Vaccine Safety Profile

These vaccines are all inactivated, which as you know cannot cause disease. It is essential to remind our patients about that. I think it is also good to remind patients that every medication has side effects including vaccines.  The side effects expected include pain and redness at the injection site as well as minor systemic adverse effects such as fever, headache, and gastrointestinal upset.  It is possible, although rare that allergic reactions can occur.  The CDC reports additional rare adverse reactions including Guillain-Barré syndrome, chronic fatigue syndrome, neurologic disorders, rheumatoid arthritis, type 1 diabetes, and autoimmune disease have been reported, but upon investigation no causal association have been found.

 

This post was written by Dr. Jennifer Girotto, the Assistant Department Head and Clinical Professor of Pharmacy Practice at the University of Connecticut School of Pharmacy.   She specializes in pediatric infectious diseases and immunizations for all aged patients. Her goal is to provide timely, evidence-based insights that support pharmacists, other healthcare professionals, and trainees in improving patient care.