Early onset sepsis calculator implementation is associated with reduced healthcare utilization and financial costs in late preterm and term newborns

This single-center before-after EOS calculator implementation study was conducted in a Dutch nonacademic teaching hospital with a mother-child unit and a neonatal ward. The hospital provides care up to level II special care for stable or moderately ill newborns[11] and admits newborns for various reasons. Our study compared two single-year birth cohorts. We screened all newborns born in our hospital from January 1, 2014, through December 31, 2014 (pre-implementation cohort), and from April 1, 2016, through March 31, 2017 (post-implementation cohort) (Fig. 1). We evaluated all births at or after 35 weeks of gestation and included newborns admitted for pediatric care within 3 days after birth. The current study is a post hoc analysis of our implementation study, which focused on the rate of empiric antibiotic treatment in the entire birth cohort [3]. For the current analysis, we focused on admitted newborns, because it is the population susceptible to EOS care utilization and associated costs.

Before implementation, newborns born at our hospital were screened for maternal risk factors and clinical symptoms by the attending staff from the mother-child unit. Maternal EOS risk factors warranting pediatric evaluation included prolonged rupture of membranes (more than 18 hours), maternal fever (38 °C or higher), prematurity, and positive maternal GBS status. Newborns requiring evaluation or care by pediatric staff for any reason were admitted for hospital care, either at the mother-child unit or neonatal ward. Newborns not admitted for hospital care accompanied mother in the mother-child unit or were discharged home.

Before implementation, a newborn at risk for EOS was assigned observation on vital signs or treatment with empiric antibiotics. This arbitrary decision was made by the attending physician, based on the combination of maternal EOS risk factors, physical examination, and/or results of complete blood count (CBC) and C-reactive protein (CRP). Within the study population, prematurity was defined as birth at 35 to 37 weeks’ gestation. If born between 35 weeks and 35 weeks and 6 days of gestation, newborns were always admitted to the neonatal ward. Without other risk factors or clinical symptoms, prematurity alone was not a reason to start empiric antibiotic treatment per se. If default empiric antibiotic therapy was started, it consisted of intravenous gentamicin and amoxicillin, followed by intravenous amoxicillin/clavulanic acid after 72 hours if not discontinued. Before the start of antibiotic treatment, blood was drawn for a CBC, CRP, and blood culture. A gentamicin serum concentration was determined and repeated if necessary. CBC and CRP were repeated after 48–72 hours of antibiotic treatment. In case of a negative blood culture after 3 days of treatment, antibiotic treatment was either stopped, or continued for clinical reasons, per discretion of the attending physician. In case of a positive blood culture, antibiotic treatment was continued for at least 7 days from start. If continued despite a negative culture, treatment was continued for 7 days.

After implementation of the EOS calculator, each birth was screened for maternal EOS risk factors and clinical symptoms, as before implementation. In case of 1 or more maternal EOS risk factors or if the newborn showed any clinical signs of EOS, prompt clinical evaluation of the newborn followed, using the EOS calculator. Based on the EOS risk calculation, in our hospital, two options were possible: either start empiric antibiotics at the neonatal ward or perform routine control of vital parameters every 3 hours at the maternal-child or neonatal ward for at least 24 hours. The EOS sepsis calculator recommendation obtaining a blood culture without starting antibiotic treatment was incongruent with our practice, and this recommendation was therefore followed by the second option. In case of antibiotic treatment, treatment protocol was equal to before implementation, as described above. Treating physicians were free to deviate from the recommendation by the calculator.

Data were obtained electronically from the clinical, pharmaceutical, and financial hospital registration and billing systems. For the first outcome, EOS-related healthcare utilization, we included three groups of clinical outcomes: outcomes related to hospital length of stay, outcomes related to relevant laboratory tests (blood cultures; complete or partial blood counts; CRP; gentamicin serum concentration), and outcomes regarding (empiric) antibiotic treatment for EOS (start of antibiotic treatment, number of antibiotic days). For the second outcome, defined as financial costs related to EOS healthcare, we retrieved for each group of clinical outcomes the related costs from the hospital billing administration and calculated the combined financial cost. Costs associated with EOS-related antibiotics were calculated using costs for antibiotics in the protocol for suspected EOS described above. Because in-house billing costs were not different between the mother-child unit and the neonatal ward, these costs were not separated. To insulate our analysis from temporal cost changes during the study timeframe, we used 2017 in-house billing costs throughout analysis for both cohorts. Costs in this study represent actual cost of care, rather than final billing charges.

Data from newborns hospitalized before implementation were compared with data from newborns hospitalized after implementation. Subgroup analyses were performed for term and preterm newborns. We also compared newborns with and without antibiotic treatment. Categorical variables were reported as (relative) frequencies with and compared with chi-square analysis. Continuous variables were reported as means with standard deviation (SD) to provide meaningful outcome measures and compared using Welch two-sample t-test, which is appropriate for skewed distributions [12‐14]. All analyses were performed using R version 3.5.2 (R Foundation, Vienna, Austria).

The year after implementation involved 1877 births at or after 35 weeks of gestation of which 827 (44.1%) were admitted for pediatric care in the first three days after birth, compared with 2076 births and 881 (42.4%) admissions before implementation. All admitted newborns were included in the analysis. Fifty of 827 (6.0%) admitted newborns were started on empiric antibiotics for suspected EOS after implementation, compared with 100 of 881 (11.4%) before implementation (P < 0.001). The rate of prematurity was comparable in both cohorts (12.1% after versus 11.7% before implementation, P = 0.798).

Healthcare utilization was assessed for three clinical outcome groups (Table 1 and Fig. 2). Mean length of stay did not differ significantly between the two cohorts in the overall study sample but was 0.37 days shorter after implementation among term newborns specifically, (P = 0.005). We found a significant reduction in mean number of EOS-related laboratory tests per newborn after implementation (P < 0.001, Table 1), including fewer blood cultures, blood counts, CRP, and gentamicin serum concentration tests (P ≤ 0.001). The use of antibiotic treatment was significantly lower after implementation (number of antibiotic days, P = 0.009). Start of empiric antibiotics in at-risk newborns, independent of implementation, was associated with significant more EOS healthcare utilization (Table 2).

Mean costs related to length of stay did not differ significantly between cohorts in the overall population but were significantly lower after implementation in the subpopulation of term newborns (Table 1 and Fig. 2). Mean costs associated with EOS-related laboratory tests and the use of empiric antibiotics were significantly lower after implementation (36.8€ vs 24.9€; P < 0.001 and 1.54€ vs 0.96€; P = 0.008, respectively). Mean combined cost associated with EOS-related care per included newborn did not differ between cohorts in the overall population but were significantly lower after implementation among term newborns specifically (2248€ vs 2041€; P = 0.020). Combined mean costs were dominated by costs related to length of stay, which accounted for 98.5% of combined costs after implementation and 99.0% before implementation.

A total of four culture-confirmed EOS cases occurred during the study period, two before and two after implementation. The mean combined costs associated with EOS-related care for these cases were €7415 per newborn. Culture-confirmed EOS represented 0.7% of total cost associated with EOS-related care in the entire study period.