Treatment of Bacteremic UTIs in Neonates: Is Oral Step-Down Therapy Safe?

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By Sarah Feeley PharmD Candidate

Oral antibiotic step-down is an antimicrobial stewardship effort utilized in infectious disease treatments. However, in neonates oral step-down therapy for bacteremic urinary tract infections (UTIs) has not been recommended in guidelines due to concerns of the seriousness of the bacteremia. But there’s been emerging evidence supporting the safe use of this practice in the neonatal population.1

In the April issue of the Journal of the Pediatric Infectious Disease Society, Greenhow and colleagues published their experience at Kaiser Permanente in Northern California transitioning from parenteral to oral antibiotics in neonates with bacteremic UTIs. This retrospective cohort evaluated outcomes of 49 full-term neonates aged 7 to 28 days with bacteremic UTIs from January 1, 2010, to December 31, 2024.1 Importantly, in addition to excluding those born premature, they also excluded those with meningitis. They compared the outcomes of those who received parenteral followed by oral antibiotic therapy (n=41) versus prolonged parenteral antibiotic courses (n=8).1 The primary pathogen identified was Escherichia coli (98%) and one case of Enterococcus faecalis.1 Cephalexin and amoxicillin were the most common oral antibiotic treatments used (Table 1 displays all oral antibiotics received).1

Table 1: Oral Antibiotics for Step-Down 1

Aminopenicillin +/- Beta-lactamase inhibitors Amoxicillin (23%)

Amoxicillin-clavulanate (2%)
Cephalosporins 1st generation: Cephalexin (30%)

3rd generation: Cefdinir (17%) and cefixime (4%)
Fluoroquinolones Ciprofloxacin (6%)

Two neonates from the parenteral to oral antibiotic group were found to have relapsed UTI without bacteremia; however, both were found to have vesicoureteral reflux.1 There were no cases of relapses of bacteremia or hospital readmission within 30 days of the index episode.1 The authors report that parenteral to oral treatment resulted in reduced duration of parenteral antibiotic use (3.7 days vs 11 days; P=0.01) and decreased length of hospitalization (2.9 days vs 8.8; P=0.01).1 When considering implementation, it’s important to note that 90% of neonates were treated with total courses for ≥10 days, and no treatment course was <9 days.1

What other evidence supports oral step-down treatment?

A multicenter retrospective cohort study published by Schroeder and colleagues evaluated 251 infants <90 days old (47% ≤28 days old) with bacteremic UTIs to determine predictors of duration of parenteral treatment and association between duration of parenteral treatment and relapse within 30 days.2 Patients were excluded if they were treated for meningitis. They found no significant difference in the duration of parenteral antibiotics in infants with and without relapse (8.2 vs 7.8 days; P=0.81). 2

Another multicenter retrospective cohort by Desai and colleagues evaluated 115 infants ≤60 days old (52% ≤28 days old) with bacteremic UTIs to determine the association between parenteral antibiotic duration and outcomes.3  Patients treated for meningitis were excluded. They found parenteral treatment durations of ≤7 days versus >7 days had no significant difference in the 30-day UTI recurrence (3% versus 7%; adjusted relative risk [aRR] 1.9; 95% confidence interval [CI], 0.3-11.6) or 30-day all-cause hospitalization (10% versus 16%; aRR 1.2; 95% CI, 0.4-3.9).3 It was also noted that infants who had worse clinical presentation, growth of non-E.coli organisms, and prolonged bacteremia were more likely to receive prolonged courses of parenteral antibiotics.

A systematic review of 18 studies in infants aged ≤90 days included the bacteremic UTI cohorts by Desai and Schroeder, along with several smaller mixed studies. In the mixed bacteremic and non-bacteremic cohorts, 246 infants had bacteremic UTIs, and 94% had favorable outcomes with early transition to oral therapy.4 In the studies that reported recurrences, infants with prolonged bacteremia received longer IV courses, severe UTI-related complications were rare, and most recurrences occurred in infants with vesicoureteral reflux or other urinary tract abnormalities, suggesting those underlying anatomic issues may have had some contribution.4

What do guidelines are recommended for treatment of bacteremic UTI?

In 2021, the American Academy of Pediatrics (AAP) released practice guidelines for the management of UTIs in well-appearing febrile infants 8 to 60 days old.5 They recommend treatment with parenteral antibiotics for bacteremic UTIs in neonates aged 8 to 28 days. Specifically,

Bacteremic UTI Empiric Treatments:

  • Age 8 to 28 days: IV/IM ampicillin plus ceftazidime or gentamicin
  • Age 22 to 28 days: IV/IM Ceftriaxone

Parenteral antibiotics can be transitioned to appropriate oral options once blood cultures are negative (usually after 24 to 36 hours). It is important to ensure that the infant is clinically improving (e.g., feeding, afebrile) 5 The 2024 Report of the Committee on Infectious Diseases of the AAP (AAP Redbook) currently recommends 10 days for total therapy duration, but this can be extended to 14 days depending on the responsible pathogen and the neonates’ clinical response. 5,6

Although not from the US, in 2025 the European Society of Pediatric Infectious Disease (ESPID) released updated recommendations that include oral transition for neonatal bacteruria. Specifically, they recommend that neonates and infants <2 months with bacteremic UTI be treated with initial IV antibiotics and transitioned to oral after ≤7 days once afebrile, well-appearing and tolerating oral intake for a total course of 10-14 days.7

What does this mean for Pharmacists in practice?

Pharmacists in the inpatient setting should be aware of this emerging evidence that supports oral step-down for treatment of bacteremic UTIs in neonates. When evaluating if oral step-down is appropriate for the patient, the neonate should be afebrile, well-appearing, tolerating oral intake, and have negative blood cultures for 24 to 36 hours prior to transitioning. The total duration of treatment would then be 10 to 14 days depending on the pathogen and their clinical status. For those outpatient pharmacists helping these patients transition to home, if there are any questions or concerns, it’s important to call the provider to verify that the dosing is correct for the indication since neonates are a vulnerable patient population. It’s also important to counsel the parents on how to administer the medication, proper storage conditions, and potential side effects of the antibiotic.

The oral step-down agents that have shown to be successful, if determined to be susceptible, include amoxicillin, amoxicillin-clavulanate, cephalexin, cefixime, cefdinir, and ciprofloxacin. Fluoroquinolones, like ciprofloxacin, should be reserved for UTIs when no other oral option is available, such as multi-drug-resistant bacteria, gram-negative bacteremia resistant to beta-lactams and other antimicrobial classes or Pseudomonas aeruginosa UTIs.8

Neonates may benefit from oral step-down therapy to reduce the duration of parenteral treatment, shorten hospital stays, and lower healthcare costs. Additionally, from an antimicrobial stewardship perspective, the implementation of oral step-down therapy may also lead to a reduced risk of resistance and nosocomial infections, catheter-related complications.

About the author: Sarah Feeley, is a Doctor of Pharmacy candidate at the University of Connecticut. This article was written as part of her Advanced Pharmacy Practice Experience under guidance from her professor, Jennifer Girotto PharmD, BCPPS, BCIBP, who also reviewed and edited this piece.

References:

  1. Greenhow TL, Amanjee K, Obrutu O, Weintraub MR, Caro D. Early transition from parenteral to oral antibiotics for neonates with bacteremic urinary tract infections. Journal of the Pediatric Infectious Diseases Society. 2026;15(4). doi: 10.1093/jpids/piag021.
  2. Schroeder AR, Shen MW, Biondi EA, et al. Bacteraemic urinary tract infection: Management and outcomes in young infants. Arch Dis Child. 2016;101(2):125–130. doi: 10.1136/archdischild-2014-307997.
  3. Desai S, Aronson PL, Shabanova V, et al. Parenteral antibiotic therapy duration in young infants with bacteremic urinary tract infections. Pediatrics. 2019;144(3):e20183844. doi: 10.1542/peds.2018–3844. Epub 2019 Aug 20. doi: 10.1542/peds.2018-3844.
  4. Hikmat S, Lawrence J, Gwee A. Short intravenous antibiotic courses for urinary infections in young infants: A systematic review. Pediatrics. 2022;149(2). doi: 10.1542/peds.2021-052466.
  5. Pantell RH, Roberts KB, Adams WG, et al. Evaluation and management of well-appearing febrile infants 8 to 60 days old. Pediatrics. 2021;148(2):e2021052228. doi: 10.1542/peds.2021–052228. Epub 2021 Jul 19. doi: 10.1542/peds.2021-052228.
  6. Committee on Infectious Diseases, American Academy of Pediatrics, Kimberlin DW, Banerjee R, Barnett ED, Lynfield R, Sawyer MH. Serious neonatal bacterial infections caused by enterobacterales (including septicemia and meningitis). 2024. doi: https://doi.org/10.1542/9781610027373-S3_005_002.
  7. Bryant PA, Bitsori M, Vardaki K, Vaezipour N, Khan M, Buettcher M. Guidelines for complicated urinary tract infections in children: A review by the european society for pediatric infectious diseases. Pediatr Infect Dis J. 2025;44(6):e211–e223. doi: 10.1097/INF.0000000000004790.
  8. Red Book: 2021–2024 Report of the Committee on Infectious Diseases, Committee on Infectious Diseases, American Academy of Pediatrics,&nbsp, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH. Fluoroquinolones. 2021. doi: https://doi.org/10.1542/9781610025782-S4_001_002.