Antibiotic Discontinuation 24 h After Neonatal Late-Onset Sepsis Work-Up—A Validated Decision Tree Model

Abstract

Objectives: Neonatal late-onset sepsis work-up is a frequent occurrence in every neonatal department. Blood cultures are the diagnostic gold standard, however, a negative culture prior to 48–72 h is often considered insufficient to exclude sepsis. We aimed to develop a decision tree which would enable exclusion of late-onset sepsis within 24 h using clinical and laboratory variables.Study Design: Infants evaluated for late-onset sepsis during the years 2016–2019, without major malformations, in a tertiary neonatal center were eligible for inclusion. Blood cultures and clinical and laboratory data were extracted at 0 and 24 h after sepsis work-up. Infants with bacteriologically confirmed late-onset sepsis were compared to matched control infants. Univariate logistic regression identified potential risk factors. A decision tree based on Chi-square automatic interaction detection methodology was developed and validated.Results: The study cohort was divided to a development cohort (105 patients) and a validation cohort (60 patients). At 24 h after initial evaluation, the best variables to identify sepsis were C-reactive protein > 0.75 mg/dl, neutrophil-to-lymphocyte ratio > 1.5 and sick-appearance at 24 h. Use of these 3 variables together with blood culture status at 24 h, enabled identification of all infants that eventually developed sepsis through the decision tree model. Our decision tree has an area under the receiver operating characteristic curve of 0.94 (95% CI: 0.90–0.98).Conclusions: In non-sick appearing infants with a negative blood culture at 24 h and normal laboratory values, sepsis is highly unlikely and discontinuing antibiotics after 24 h is a viable option.

Implementation of a 24-hour empiric antibiotic duration for negative early-onset sepsis evaluations to reduce early antibiotic exposure in premature infants

“…29 Several studies support the safety of the 24-hour rule in wellappearing term infants, but these studies used clinical or laboratory criteria to guide the early discontinuation of antibiotics for low-risk infants. 18,30,31 Time to positivity >36 hours is common with coagulase-negative staphylococci (CONS) isolation, 28 so empiric treatment for >24 hours is appropriate for late-onset neonatal sepsis, many of which are caused by CONS. 32 In our center, urine culture results also routinely require 24-36 hours for a positive result.…”

“…17 Many NICUs use 48 hours of empiric antibiotics in EOS evaluations, yet the growth of most EOS pathogens in culture in most cases are identified within 24 hours. 8,[18][19][20] The duration of antimicrobial activity extends hours to days beyond the last dose for some antibiotics in preterm infants, including ampicillin and gentamicin. 21,22 To reduce the length of early antibiotic exposure for neonates, we implemented a change in the unit guideline to shorten the duration of empiric EOS antibiotic coverage from 48 (last dose at 36 hours) to 24 hours (last dose at 12 hours) while ensuring no adverse effects.…”