Trends in C-Reactive Protein Use in Early-Onset Sepsis Evaluations and Associated Antibiotic Use

Abstract

To determine the prevalence of C-reactive protein (CRP) use in early-onset sepsis (EOS) evaluations in neonatal intensive care units (NICUs) across the United States over time and to determine the association between CRP use and antibiotic use. A retrospective cohort study of NICUs contributing data to Premier Healthcare Database from 2009 through 2021. EOS evaluation was defined as a blood culture charge <3 days after birth. CRP use for each NICU was calculated as the proportion of infants with a CRP test obtained <3 days after birth among those undergoing an EOS evaluation and categorized as, low (<25%); medium-low (25 to <50%), medium-high (50 to <75%), and high (≥75%). Outcomes included antibiotic use and mortality ≤7 days after birth. Among 572 NICUs, CRP use varied widely and was associated with time. The proportion of NICUs with high CRP use decreased from 2009 to 2021 (24.7% vs. 17.4%, P <0.001), and low CRP use NICUs increased (47.9% vs. 64.8%, P <0.001). Compared with low use NICUs, high use NICUs more frequently continued antibiotics >3 days (10% vs. 25%, P<0.001). This association persisted in multivariable-adjusted regression analyses (aRR 1.95, 95%CI 1.54, 2.48). Risk of mortality was not different in high use NICUs (adjusted risk difference -0.02%, 95%CI -0.04%, 0.0008%). CRP use in EOS evaluations varied widely across NICUs. High CRP use was associated with prolonged antibiotic therapy but not mortality ≤7 days after birth. Reducing routine CRP use in EOS evaluations may be a target for neonatal antibiotic stewardship efforts.