Association of Use of the Neonatal Early-Onset Sepsis Calculator With Reduction in Antibiotic Therapy and Safety

Abstract

The neonatal early-onset sepsis (EOS) calculator is a clinical risk stratification tool increasingly used to guide the use of empirical antibiotics for newborns. Evidence on the effectiveness and safety of the EOS calculator is essential to inform clinicians considering implementation.OBJECTIVE To assess the association between management of neonatal EOS guided by the neonatal EOS calculator (compared with conventional management strategies) and reduction in antibiotic therapy for newborns.DATA SOURCES Electronic searches in MEDLINE, Embase, Web of Science, and Google Scholar were conducted from 2011 (introduction of the EOS calculator model) through January 31, 2019.STUDY SELECTION All studies with original data that compared management guided by the EOS calculator with conventional management strategies for allocating antibiotic therapy to newborns suspected to have EOS were included.DATA EXTRACTION AND SYNTHESIS Following PRISMA-P guidelines, relevant data were extracted from full-text articles and supplements. CHARMS (Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) tools were used to assess the risk of bias and quality of evidence. Meta-analysis using a random-effects model was conducted for studies with separate cohorts for EOS calculator and conventional management strategies. MAIN OUTCOMES AND MEASURESThe difference in percentage of newborns treated with empirical antibiotics for suspected or proven EOS between management guided by the EOS calculator and conventional management strategies. Safety-related outcomes involved missed cases of EOS, readmissions, treatment delay, morbidity, and mortality. RESULTSThirteen relevant studies analyzing a total of 175 752 newborns were included. All studies found a substantially lower relative risk (range, 3%-60%) for empirical antibiotic therapy, favoring the EOS calculator. Meta-analysis revealed a relative risk of antibiotic use of 56% (95% CI, 53%-59%) in before-after studies including newborns regardless of exposure to chorioamnionitis. Evidence on safety was limited, but proportions of missed cases of EOS were comparable between management guided by the EOS calculator (5 of 18 [28%]) and conventional management strategies (8 of 28 [29%]) (pooled odds ratio, 0.96; 95% CI, 0.26-3.52; P = .95).CONCLUSIONS AND RELEVANCE Use of the neonatal EOS calculator is associated with a substantial reduction in the use of empirical antibiotics for suspected EOS. Available evidence regarding safety of the use of the EOS calculator is limited, but shows no indication of inferiority compared with conventional management strategies.

Neonatal sepsis: need for consensus definition, collaboration and core outcomes

“…Markers of systemic inflammation and immune responses include serial white cell counts and immatureto-mature granulocyte (IT) ratio. [14][15][16][17] Serial full blood count values and IT ratios can predict the absence of early onset sepsis (EOS) with an AUC~0.8 and negative predictive value for proven and suspected sepsis of 99% and 78%, respectively. 12 In addition, CRP and Procalcitonin demonstrate that biomarkers can be useful to shorten antibiotic treatment in patients who improve rapidly after treatment and have negative blood cultures.…”

“…[17][18][19] In addition, a recent meta-analysis and systematic review demonstrated that use of the neonatal EOS calculator is associated with a substantial reduction in the use of empirical antibiotics for suspected EOS. 16 In view of the insensitivity of blood cultures alone to define neonatal infection, other techniques hold promise such as 16s rRNA and PCR which detects <3 copies bacterium. Positives identified by PCR were higher than by blood culture (10 versus 5%) and when blood culture was used as control, the sensitivity and specificity of PCR was 100% and 97.85%, respectively and the index of accurate diagnosis was 0.979.…”

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

“…This may be explained by several factors. First, Gong et al used a fictitious relative reduction of 67% in empiric antibiotic treatment by implementation of the EOS calculator, which is significantly above real-world evidence in the literature [4]. Second, the predicted cost savings were based on American healthcare costs, which are relatively high compared with European countries [16].…”

“…It stratifies newborns into three levels of risk with corresponding recommendations for management: (1) no additional care, (2) obtaining a blood culture and monitor vital signs for at least 24 hours, or (3) start treatment with empiric antibiotic therapy after obtaining a blood culture [1,2]. This approach is associated with a reduction of empiric antibiotic treatment for suspected EOS between 41 and 45% compared with conventional strategies [2][3][4].…”

Authors’ reply re: Universal screening versus risk‐based protocols for antibiotic prophylaxis during childbirth to prevent early‐onset Group B streptococcal disease: a systematic review and meta‐analysis

“…Perinatal empirical therapy of newborns at risk for or with suspected early‐onset sepsis represents the main contributor to the use of antibiotics in early life 4 . There is growing concern about the effects that unnecessary exposure to antibiotics in the perinatal period may have on the future health of these children 5,6 .…”