Treatment of Urinary Tract Infections in Neonates and Young Infants: Evidence and Recommendations

Background/Objectives: Urinary tract infection (UTI) is among the most common serious bacterial infections occurring in the first 90 days of life and a leading indication for parenteral antibiotic therapy. Despite its clinical importance, no randomized trial has compared empiric antibiotic regimens, route of administration, or treatment duration specifically in this population. This review synthesizes current evidence to support rational antibiotic treatment decisions for neonates (ages 0–28 days) and young infants (ages 29–90 days), including those born prematurely. Methods: A targeted PubMed and MEDLINE search was conducted through July 2026. Studies reporting treatment outcomes, pharmacokinetic data, or antibiotic safety in infants aged 0–90 days were included. Broader pediatric data were incorporated where age-specific evidence was unavailable and are presented with explicit population caveats. Results: Escherichia coli is the predominant uropathogen across all age strata; extended-spectrum beta-lactamase (ESBL)-producing organisms account for a clinically important minority of community-acquired isolates. No comparative trial of empiric regimens existed for confirmed UTI in this age group. Shorter intravenous courses were not associated with higher 30-day recurrence rates for either nonbacteremic or bacteremic UTI after exclusion of meningitis. Intravenous-to-oral (IV-to-oral) transition with amoxicillin–clavulanate was pharmacokinetically supported and clinically safe in selected term neonates, based on indirect evidence from neonatal infection trials. Non-carbapenem therapy is appropriate for ESBL UTI without concomitant bacteremia in clinically improving infants. Exclusion of meningitis before shortening intravenous therapy or initiating oral step-down is essential, particularly in neonates ≤28 days of age. Conclusions: Short parenteral courses with timely transition to oral antibiotics are recommended in appropriately selected infants with UTI, consistent with antimicrobial stewardship principles and supported by observational evidence. The evidence base is limited, with key gaps in empiric regimen selection, management of premature infants, ESBL treatment in bacteremic patients, and optimal duration of parenteral and oral antibiotic therapy.