Martin Stocker1, Wendy van Herk2, Salhab El Helou3, Sourabh Dutta3, Frank A B A Schuerman4, Rita K van den Tooren-de Groot5, Jantien W Wieringa5, Jan Janota6,7, Laura H van der Meer-Kappelle8, Rob Moonen9, Sintha D Sie10, Esther de Vries11, Albertine E Donker12, Urs Zimmerman13, Luregn J Schlapbach14,15,16, Amerik C de Mol17, Angelique Hoffman-Haringsma18, Madan Roy19, Maren Tomaske20, René F Kornelisse21, Juliette van Gijsel22, Eline G Visser2, Frans B Plötz23, Paul Heath24, Niek B Achten23, Dirk Lehnick25, Annemarie M C van Rossum2. 1. Department of Paediatrics, Neonatal and Paediatric Intensive Care Unit, Children's Hospital Lucerne, Lucerne, Switzerland. 2. Department of Paediatrics, Division of Paediatric Infectious Diseases & Immunology, Erasmus Medical Centre, University Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands. 3. Division of Neonatology, McMaster University Children's Hospital, Hamilton Health Sciences, Hamilton, Ontario, Canada. 4. Department of Neonatal Intensive Care Unit, Isala Women and Children's Hospital, Zwolle, The Netherlands. 5. Department of Paediatrics, Haaglanden Medical Centre, "s Gravenhage, The Netherlands. 6. Department of Obstetrics and Gynocology, Second Medical Faculty, Motol University Hospital, Prague, Czech Republic. 7. First Medical Faculty, Czech Republic and Institute of Pathological Physiology, Prague, Czech Republic. 8. Department of Neonatology, Reinier de Graaf Gasthuis, Delft, The Netherlands. 9. Department of Neonatology, Zuyderland Medical Centre, Heerlen, The Netherlands. 10. Department of Neonatology, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. 11. Department of Paediatrics, Jeroen Bosch Hospital, "s-Hertogenbosch, The Netherlands. 12. Department of Paediatrics, Maxima Medical Centre, Veldhoven, The Netherlands. 13. Department of Paediatrics, Kantonsspital Winterthur, Winterthur, Switzerland. 14. Paediatric Critical Care Research Group, Child Health Research Centre, University of Queensland, Brisbane, Australia. 15. Padiaitric Intensive Care Unit, Queensland Children's Hospital, Brisbane, Australia. 16. University Children's Hospital Zurich and University of Zurich, Zurich, Switzerland. 17. Department of Neonatology, Albert Schweitzer Hospital, Dordrecht, The Netherlands. 18. Department of Neonatology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands. 19. Department of Neonatology, St. Josephs Healthcare, Hamilton Health Sciences, Hamilton, Ontario, Canada. 20. Department of Paediatrics, Stadtspital Triemli, Zürich, Switzerland. 21. Department of Paediatrics, Division of Neonatology, Erasmus Medical Centre, University Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands. 22. Therapeuticum Utrecht, Utrecht, The Netherlands. 23. Department of Pediatrics, Tergooi Hospital, Blaricum, The Netherlands. 24. Department of Paediatric Infectious Disease, St George's University Hospital, London, United Kingdom. 25. Department of Health Sciences and Medicine, Head Biostatistics and Methodology, University of Lucerne, Lucerne, Switzerland.
Abstract
BACKGROUND: Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful. METHODS: We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis). RESULTS: We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis. CONCLUSIONS:Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.
RCT Entities:
BACKGROUND: Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful. METHODS: We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis). RESULTS: We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis. CONCLUSIONS: Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.
Authors: Fleur M Keij; Niek B Achten; Gerdien A Tramper-Stranders; Karel Allegaert; Annemarie M C van Rossum; Irwin K M Reiss; René F Kornelisse Journal: Front Pediatr Date: 2021-04-01 Impact factor: 3.418
Authors: Irene Doo; Lukas P Staub; Adrian Mattke; Emma Haisz; Anna Lene Seidler; Nelson Alphonso; Luregn J Schlapbach Journal: Front Pediatr Date: 2022-01-26 Impact factor: 3.418
Authors: O R E Dongen; L M van Leeuwen; P K de Groot; K Vollebregt; I Schiering; B A Wevers; S M Euser; M A van Houten Journal: Front Pediatr Date: 2021-12-10 Impact factor: 3.418