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Association of Use of the Neonatal Early-Onset Sepsis Calculator With Reduction in Antibiotic Therapy and Safety: A Systematic Review and Meta-analysis.

  • Achten, Niek B1, 2
  • Klingenberg, Claus3, 4
  • Benitz, William E5
  • Stocker, Martin6
  • Schlapbach, Luregn J7, 8, 9
  • Giannoni, Eric10
  • Bokelaar, Robin1
  • Driessen, Gertjan J A11
  • Brodin, Petter12
  • Uthaya, Sabita13
  • van Rossum, Annemarie M C14
  • Plötz, Frans B1
  • 1 Department of Pediatrics, Tergooi Hospital, Blaricum, the Netherlands. , (Netherlands)
  • 2 Faculty of Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands. , (Netherlands)
  • 3 Department of Pediatrics and Adolescence Medicine, University Hospital of North Norway, Tromsø, Norway. , (Norway)
  • 4 Paediatric Research Group, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway. , (Norway)
  • 5 Department of Pediatrics, Stanford University, Stanford, California.
  • 6 Department of Pediatrics, Children's Hospital Lucerne, Lucerne, Switzerland. , (Switzerland)
  • 7 Paediatric Critical Care Research Group, Child Health Research Centre, University of Queensland, Brisbane, Australia. , (Australia)
  • 8 Paediatric Intensive Care Unit, Queensland Children's Hospital, Brisbane, Australia. , (Australia)
  • 9 Department of Pediatrics, Bern University Hospital, University of Bern, Bern, Switzerland. , (Switzerland)
  • 10 Department Woman-Mother-Child, Clinic of Neonatology, Lausanne University Hospital, Lausanne, Switzerland. , (Switzerland)
  • 11 Department of Pediatrics, Juliana Children's Hospital, Haga Teaching Hospital, The Hague, the Netherlands. , (Netherlands)
  • 12 Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. , (Sweden)
  • 13 Section of Neonatal Medicine, Department of Medicine, Imperial College London, London, United Kingdom. , (United Kingdom)
  • 14 Department of Pediatrics, Erasmus University Medical Centre-Sophia Children's Hospital, Rotterdam, the Netherlands. , (Netherlands)
Published Article
JAMA pediatrics
Publication Date
Nov 01, 2019
DOI: 10.1001/jamapediatrics.2019.2825
PMID: 31479103


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. 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. 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. 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. 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. The 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. Thirteen 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). 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.

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