International Journal of Infectious Diseases (May 2024)
Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: A prospective study of diagnostic accuracy
- Nina S. Groeneveld,
- Sabine E. Olie,
- Douwe H. Visser,
- Linde Snoek,
- Diederik van de Beek,
- Matthijs C. Brouwer,
- Merijn W. Bijlsma,
- Rolanda Baars,
- Ron van Beek,
- Vincent Bekker,
- Maartje van den Berg,
- Geert Jan Blok,
- Mijke Breukels,
- Alwin F.J. Brouwer,
- Luçan C. Delemarre,
- Anouk Dings,
- Rienus A. Doedens,
- Stefan M. van Dorth,
- Gertjan Driessen,
- Hester M. Havers,
- Jojanneke Heidema,
- Marieke A.C. Hemels,
- Maartje E.N. van den Heuvel,
- Marlies van Houten,
- Flip van der Hulst,
- Monique A.M. Jacobs,
- Arieke Janse,
- Miranda de Jong,
- Anton H. van Kaam,
- Ageeth Kaspers,
- Merel N. van Kassel,
- Anne A.M.W. van Kempen,
- Karen Korbeek,
- Kristine Klúčovská,
- René F. Kornelisse,
- Taco W. Kuijpers,
- Elisabeth van Leeuwen,
- Jeannette von Lindern,
- Karen Van Mechelen,
- Clemens B. Meijssen,
- Jeroen Noordzij,
- Annemarie Oudshoorn,
- Frans B. Plötz,
- Maarten Rijpert,
- Maaike van Rossem,
- Machteld van Scherpenzeel,
- Renske Cornelisse-van Vugt,
- George Shabo,
- Nina M. van Sorge,
- Jacqueline van der Sluijs,
- Carmen Lorente Flores,
- Jacqueline U.M. Termote,
- Gerdien A. Tramper-Stranders,
- Gavin W. ten Tusscher,
- Mirjam van Veen,
- Marlies Vermaas,
- Marjoke Verweij,
- Wouter J. de Waal,
- Anne-Marie van Wermeskerken,
- Janneke Wilms,
- Tom F.W. Wolfs
Affiliations
- Nina S. Groeneveld
- Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Sabine E. Olie
- Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Douwe H. Visser
- Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, The Netherlands; Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands
- Linde Snoek
- Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Diederik van de Beek
- Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Matthijs C. Brouwer
- Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Merijn W. Bijlsma
- Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatrics, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Address correspondence to: Merijn W. Bijlsma, Department of Paediatrics, Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, 1100DD The Netherlands. Tel.: +316-50100769.
- Rolanda Baars
- Department of Paediatrics, St. Jansdal Hospital, Harderwijk, Netherlands
- Ron van Beek
- Department of Paediatrics, Amphia Hospital, Breda, Netherlands
- Vincent Bekker
- Department of Paediatrics, Leiden University Medical Centre, Leiden, Netherlands
- Maartje van den Berg
- Department of Paediatrics, Haaglanden Medical Centre, The Hague, Netherlands
- Geert Jan Blok
- Department of Neonatology, Northwest Clinics, Alkmaar, Netherlands
- Mijke Breukels
- Department of Paediatrics, Elkerliek Hospital, Helmond, Netherlands
- Alwin F.J. Brouwer
- Department of Paediatrics, Hospital of Nij Smellinghe, Drachten, Netherlands
- Luçan C. Delemarre
- Department of Paediatrics, Amstelland Hospital, Amstelveen, Netherlands
- Anouk Dings
- Department of Paediatrics, Gelre Hospitals, Apeldoorn, Netherlands
- Rienus A. Doedens
- Department of Paediatrics, Martini Hospital, Groningen, Netherlands
- Stefan M. van Dorth
- Department of Paediatrics, Tjongerschans Hospital, Heerenveen, Netherlands
- Gertjan Driessen
- Department of Paediatrics, Haga Hospital, The Hague, Netherlands
- Hester M. Havers
- Department of Paediatrics, Alrijne Hospital, Leiderdorp, Netherlands
- Jojanneke Heidema
- Department of Paediatrics, St. Antonius Hospital, Utrecht, Netherlands
- Marieke A.C. Hemels
- Department of Neonatology, Isala Clinics, Zwolle, Netherlands
- Maartje E.N. van den Heuvel
- Department of Paediatrics, Onze Lieve Vrouwe Gasthuis, West location, Amsterdam, Netherlands
- Marlies van Houten
- Department of Paediatrics, Spaarne Gasthuis, Haarlem, Netherlands
- Flip van der Hulst
- Department of Paediatrics, Zaans Medical Centre, Zaandam, Netherlands
- Monique A.M. Jacobs
- Department of Paediatrics, Slingeland Hospital, Doetinchem, Netherlands
- Arieke Janse
- Department of Paediatrics, Gelderse Vallei Hospital, Ede, Netherlands
- Miranda de Jong
- Department of Paediatrics, Albert Schweitzer Hospital, Dordrecht, Netherlands
- Anton H. van Kaam
- Department of Neonatology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
- Ageeth Kaspers
- Department of Paediatrics, Medisch Spectrum Twente, Twente, Netherlands
- Merel N. van Kassel
- Department of Neurology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
- Anne A.M.W. van Kempen
- Department of Paediatrics, Onze Lieve Vrouwe Gasthuis, East location, Amsterdam, Netherlands
- Karen Korbeek
- Department of Paediatrics, St. Jansdal Hospital, Harderwijk, Netherlands
- Kristine Klúčovská
- Department of Paediatrics, Treant Hospital Group, Hoogeveen, Netherlands
- René F. Kornelisse
- Department of Paediatrics, Erasmus Medical Centre, Rotterdam, Netherlands
- Taco W. Kuijpers
- Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
- Elisabeth van Leeuwen
- Department of Obstetrics and Gynaecology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
- Jeannette von Lindern
- Department of Paediatrics, Groene Hart Hospital, Gouda, Netherlands
- Karen Van Mechelen
- Department of Neonatology, Maastricht University Medical Centre, Maastricht, Netherlands
- Clemens B. Meijssen
- Department of Paediatrics, Meander Medical Centre, Amersfoort, Netherlands
- Jeroen Noordzij
- Department of Paediatrics, Reinier de Graaf Hospital, Delft, Netherlands
- Annemarie Oudshoorn
- Department of Paediatrics, Gelre Hospitals, Apeldoorn, Netherlands
- Frans B. Plötz
- Tergooi Hospital, Hilversum, Netherlands
- Maarten Rijpert
- Department of Paediatrics, Zaans Medical Centre, Zaandam, Netherlands
- Maaike van Rossem
- Department of Paediatrics, Rijnstate Hospital, Arnhem, Netherlands
- Machteld van Scherpenzeel
- Department of Paediatrics, Medical Centre Leeuwarden, Leeuwarden, Netherlands
- Renske Cornelisse-van Vugt
- Department of Paediatrics, Canisius Wilhelmina Hospital, Nijmegen, Netherlands
- George Shabo
- Department of Paediatrics, Hospital Group Twente, Twente, Netherlands
- Nina M. van Sorge
- Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands
- Jacqueline van der Sluijs
- Department of Neonatology, Maxima Medical Centre, Veldhoven, Netherlands
- Carmen Lorente Flores
- Department of Neonatology, Maxima Medical Centre, Veldhoven, Netherlands
- Jacqueline U.M. Termote
- Department of Neonatology, University Medical Centre Utrecht, Utrecht, Netherlands
- Gerdien A. Tramper-Stranders
- Department of Paediatrics, Franciscus Gasthuis, Rotterdam, Netherlands
- Gavin W. ten Tusscher
- Department of Paediatrics, Dijklander Hospital, Hoorn, Netherlands
- Mirjam van Veen
- Department of Paediatrics, Haga Hospital, The Hague, Netherlands
- Marlies Vermaas
- Department of Paediatrics, Admiraal de Ruyter Hospital, Goes, Netherlands
- Marjoke Verweij
- Department of Paediatrics, Viecuri Medical Centre, Venlo, Netherlands
- Wouter J. de Waal
- Department of Paediatrics, Diakonesse Hospital, Utrecht, Netherlands
- Anne-Marie van Wermeskerken
- Department of Paediatrics, Flevohospital, Almere, Netherlands
- Janneke Wilms
- Department of Paediatrics, Boven IJ Hospital, Amsterdam, Netherlands
- Tom F.W. Wolfs
- Department of Paediatrics, University Medical Centre Utrecht, Utrecht, Netherlands
- Journal volume & issue
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Vol. 142
p. 106970
Abstract
Objectives: We evaluated the diagnostic accuracy of cerebrospinal fluid (CSF) inflammatory markers for diagnosing bacterial meningitis in neonates with sepsis and/or meningitis. Methods: Cases were identified from a prospective multicenter study including patients aged 0-3 months with Group B Streptococcal (GBS) or Escherichia coli culture positive sepsis/meningitis. CSF CXCL10, MDC, IL-6, IL-8, IL-10, TNF- α, MIF, IL-1RA, CXCL13, IL-1β, CRP and procalcitonin concentrations were measured with Luminex technology. Results: In 61/373 patients (17%) residual CSF from the lumbar puncture was available, of whom 16 (26%) had definitive meningitis, 15 (25%) probable meningitis and 30 (49%) had sepsis. All biomarkers were detectable in CSF and showed significantly higher concentrations in definitive meningitis versus sepsis patients and six biomarkers in probable meningitis versus sepsis patients. Discrimination between definitive meningitis and sepsis was excellent for IL-1RA (area under the receiver operating characteristic curve [AUC] 0.93), TNF-α (AUC 0.92), CXCL10 (AUC 0.90), IL-1β (AUC 0.92), IL-6 (AUC 0.94), IL-10 (AUC 0.93) and a combination of IL-1RA, TNF-α, CXCL-10 and CSF leukocyte count (AUC 0.95). CSF leukocyte count remained the predictor with the highest diagnostic accuracy (AUC 0.96). Conclusion: CSF inflammatory markers can be used to differentiate between neonatal sepsis and meningitis.
