Restricting C-Reactive Protein Use in Early-Onset Neonatal Sepsis Reduces Unnecessary Antibiotic Exposure

<b>Background:</b> some consensus guidelines include C-reactive protein (CRP) in the diagnostic workup of early-onset neonatal sepsis (EOS), but its routine use remains debated due to variable diagnostic performance. The experiences and data from individual centers can help clarify its clinical utility and inform local practice. <b>Methods:</b> Retrospective analysis at a level III center assessing the impact of discontinuing routine C-reactive protein (CRP) testing for suspected early-onset sepsis (EOS). Laboratory use, antibiotic therapy, and outcomes in neonates of all gestational ages were compared before (2021-2022) and after (2024-2025) the policy change. <b>Results:</b> A total of 638 neonates were included (period 1, <i>n</i> = 348; period 2, <i>n</i> = 290). CRP testing decreased markedly (218/348 in period 1 vs. 40/290 in period 2; <i>p</i> < 0.001), alongside a significant reduction in the number of complete blood counts performed (285/348 vs. 214/290; <i>p</i> = 0.02). Concurrently, both the proportion of short antibiotic courses (≤48 h) initiated within the first 3 days of life (98/181 vs. 88/133) and the median duration of antibiotic therapy (48.0 h vs. 40.0 h; <i>p</i> < 0.001) decreased without worsening outcomes. The duration of antibiotic therapy was even shorter in infants born before 34 weeks' gestation (48.0 h vs. 37.5 h; <i>p</i> < 0.001). <b>Conclusions:</b> Restricting the use of CRP in the evaluation of EOS was associated with a reduction in unnecessary antibiotic exposure. This strategy may be considered a core component of neonatal antibiotic stewardship programs.