Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: a prospective study of diagnostic accuracy

NOGBS study group; 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; NOGBS study group:

doi:10.1016/j.ijid.2024.02.013

Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: a prospective study of diagnostic accuracy

NOGBS study group
, 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, NOGBS study group:

University of Amsterdam
Amsterdam Reproduction and Development
St Jansdal Hospital
Amphia ziekenhuis
Leiden University
Haaglanden Medisch Centrum
North West Hospital Group
Elkerliek Hospital
Nij Smellinghe Hospital
Amstelland Hospital
Gelre Ziekenhuizen
Martini Ziekenhuis
Tjongerschans Hospital
Haga Ziekenhuis
Department of Urology, Alrijne Hospital, Leiderdorp, The Netherlands
St. Antonius Hospital
Isala Clinics
locatie West Previously Sint Lucas Andreas Ziekenhuis
Spaarne Gasthuis
Zaans Medisch Centrum
Slingeland Hospital
Ziekenhuis Gelderse Vallei
Albert Schweitzer Hospital, Dordrecht.
Amsterdam University Medical Centers
Medisch Spectrum Twente (MST)
Treant Care Group
Erasmus University Rotterdam
Groene Hart Hospital
University of Limburg
Meander Medical Center
Reinier de Graaf Groep
Tergooi Hospital
Rijnstate Hospital
Medical Centre Leeuwarden
Canisius Wilhelmina Hospital
Hospital Group Twente
Maxima Medical Centre
Utrecht University
Franciscus Gasthuis & Vlietland Hospital
Department of Emergency Medicine, Dijklander Hospital, Hoorn, the Netherlands
Admiraal de Ruyter Hospital
VieCuri Medisch Centrum
Diakonesse Hospital
Flevo Hospital
BovenIJ Hospital

Research output: Contribution to journal › Article › Academic › peer-review

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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 CXCL-10, MDC, IL6, 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) CXCL-10 (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.

Original language	English
Article number	106970
Journal	International journal of infectious diseases : IJID
Volume	142
Early online date	21 Feb 2024
DOIs	https://doi.org/10.1016/j.ijid.2024.02.013
Publication status	Published - 1 May 2024

Keywords

Cerebrospinal fluid
Diagnostic
Neonatal meningitis
Neonatal sepsis

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NOGBS study group, Baars, R., van Beek, R., Bekker, V., van den Berg, M., Blok, G. J., Breukels, M., Brouwer, A. F. J., Delemarre, L. C., Dings, A., Doedens, R. A., van Dorth, S. M., Driessen, G., Havers, H. M., Heidema, J., Hemels, M. A. C., van den Heuvel, M. E. N., van Houten, M., van der Hulst, F., ... NOGBS study group: (2024). Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: a prospective study of diagnostic accuracy. International journal of infectious diseases : IJID, 142, Article 106970. https://doi.org/10.1016/j.ijid.2024.02.013

@article{10255224239c461e80ea765d4a8f3a05,

title = "Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: a prospective study of diagnostic accuracy",

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 CXCL-10, MDC, IL6, 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) CXCL-10 (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.",

keywords = "Cerebrospinal fluid, Diagnostic, Neonatal meningitis, Neonatal sepsis",

author = "\{NOGBS study group\} and Groeneveld, \{Nina S\} and Olie, \{Sabine E\} and Visser, \{Douwe H\} and Linde Snoek and \{van de Beek\}, Diederik and Brouwer, \{Matthijs C\} and Bijlsma, \{Merijn W\} and Rolanda Baars and \{van Beek\}, Ron and Vincent Bekker and \{van den Berg\}, Maartje and Blok, \{Geert Jan\} and Mijke Breukels and Brouwer, \{Alwin F. J.\} and Delemarre, \{Lu{\c c}an C.\} and Anouk Dings and Doedens, \{Rienus A.\} and \{van Dorth\}, \{Stefan M.\} and Gertjan Driessen and Havers, \{Hester M.\} and Jojanneke Heidema and Hemels, \{Marieke A. C.\} and \{van den Heuvel\}, \{Maartje E. N.\} and \{van Houten\}, Marlies and \{van der Hulst\}, Flip and Jacobs, \{Monique A. M.\} and Arieke Janse and \{de Jong\}, Miranda and \{van Kaam\}, \{Anton H.\} and Ageeth Kaspers and \{van Kassel\}, \{Merel N.\} and \{van Kempen\}, \{Anne A. M. W.\} and Karen Korbeek and Kristine Kl{\'u}{\v c}ovsk{\'a} and Kornelisse, \{Ren{\'e} F.\} and Kuijpers, \{Taco W.\} and \{van Leeuwen\}, Elisabeth and \{von Lindern\}, Jeannette and \{van Mechelen\}, Karen and Meijssen, \{Clemens B.\} and Jeroen Noordzij and Annemarie Oudshoorn and Pl{\"o}tz, \{Frans B.\} and Maarten Rijpert and \{van Rossem\}, Maaike and \{van Scherpenzeel\}, Machteld and \{Cornelisse-van Vugt\}, Renske and George Shabo and \{van Sorge\}, \{Nina M.\} and \{van der Sluijs\}, Jacqueline and \{Lorente Flores\}, Carmen and Termote, \{Jacqueline U. M.\} and Tramper-Stranders, \{Gerdien A.\} and \{ten Tusscher\}, \{Gavin W.\} and \{van Veen\}, Mirjam and Marlies Vermaas and Marjoke Verweij and \{de Waal\}, \{Wouter J.\} and \{van Wermeskerken\}, Anne-Marie and Janneke Wilms and \{NOGBS study group:\} and Wolfs, \{Tom F. W.\}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = may,

day = "1",

doi = "10.1016/j.ijid.2024.02.013",

language = "English",

volume = "142",

journal = "International journal of infectious diseases : IJID",

issn = "1201-9712",

publisher = "Elsevier",

}

NOGBS study group, Baars, R, van Beek, R, Bekker, V, van den Berg, M, Blok, GJ, Breukels, M, Brouwer, AFJ, Delemarre, LC, Dings, A, Doedens, RA, van Dorth, SM, Driessen, G, Havers, HM, Heidema, J, Hemels, MAC, van den Heuvel, MEN, van Houten, M, van der Hulst, F, Jacobs, MAM, Janse, A, de Jong, M, van Kaam, AH, Kaspers, A, van Kassel, MN, van Kempen, AAMW, Korbeek, K, Klúčovská, K, Kornelisse, RF, Kuijpers, TW, van Leeuwen, E, von Lindern, J, van Mechelen, K, Meijssen, CB, Noordzij, J, Oudshoorn, A, Plötz, FB, Rijpert, M, van Rossem, M, van Scherpenzeel, M, Cornelisse-van Vugt, R, Shabo, G, van Sorge, NM, van der Sluijs, J, Lorente Flores, C, Termote, JUM, Tramper-Stranders, GA, ten Tusscher, GW, van Veen, M, Vermaas, M, Verweij, M, de Waal, WJ, van Wermeskerken, A-M, Wilms, J & NOGBS study group: 2024, 'Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: a prospective study of diagnostic accuracy', International journal of infectious diseases : IJID, vol. 142, 106970. https://doi.org/10.1016/j.ijid.2024.02.013

Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: a prospective study of diagnostic accuracy. / NOGBS study group; Baars, Rolanda; van Beek, Ron et al.
In: International journal of infectious diseases : IJID, Vol. 142, 106970, 01.05.2024.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis

T2 - a prospective study of diagnostic accuracy

AU - NOGBS study group

AU - Groeneveld, Nina S

AU - Olie, Sabine E

AU - Visser, Douwe H

AU - Snoek, Linde

AU - van de Beek, Diederik

AU - Brouwer, Matthijs C

AU - Bijlsma, Merijn W

AU - Baars, Rolanda

AU - van Beek, Ron

AU - Bekker, Vincent

AU - van den Berg, Maartje

AU - Blok, Geert Jan

AU - Breukels, Mijke

AU - Brouwer, Alwin F. J.

AU - Delemarre, Luçan C.

AU - Dings, Anouk

AU - Doedens, Rienus A.

AU - van Dorth, Stefan M.

AU - Driessen, Gertjan

AU - Havers, Hester M.

AU - Heidema, Jojanneke

AU - Hemels, Marieke A. C.

AU - van den Heuvel, Maartje E. N.

AU - van Houten, Marlies

AU - van der Hulst, Flip

AU - Jacobs, Monique A. M.

AU - Janse, Arieke

AU - de Jong, Miranda

AU - van Kaam, Anton H.

AU - Kaspers, Ageeth

AU - van Kassel, Merel N.

AU - van Kempen, Anne A. M. W.

AU - Korbeek, Karen

AU - Klúčovská, Kristine

AU - Kornelisse, René F.

AU - Kuijpers, Taco W.

AU - van Leeuwen, Elisabeth

AU - von Lindern, Jeannette

AU - van Mechelen, Karen

AU - Meijssen, Clemens B.

AU - Noordzij, Jeroen

AU - Oudshoorn, Annemarie

AU - Plötz, Frans B.

AU - Rijpert, Maarten

AU - van Rossem, Maaike

AU - van Scherpenzeel, Machteld

AU - Cornelisse-van Vugt, Renske

AU - Shabo, George

AU - van Sorge, Nina M.

AU - van der Sluijs, Jacqueline

AU - Lorente Flores, Carmen

AU - Termote, Jacqueline U. M.

AU - Tramper-Stranders, Gerdien A.

AU - ten Tusscher, Gavin W.

AU - van Veen, Mirjam

AU - Vermaas, Marlies

AU - Verweij, Marjoke

AU - de Waal, Wouter J.

AU - van Wermeskerken, Anne-Marie

AU - Wilms, Janneke

AU - NOGBS study group:

AU - Wolfs, Tom F. W.

PY - 2024/5/1

Y1 - 2024/5/1

N2 - 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 CXCL-10, MDC, IL6, 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) CXCL-10 (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.

AB - 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 CXCL-10, MDC, IL6, 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) CXCL-10 (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.

KW - Cerebrospinal fluid

KW - Diagnostic

KW - Neonatal meningitis

KW - Neonatal sepsis

UR - https://www.scopus.com/pages/publications/85188721736

U2 - 10.1016/j.ijid.2024.02.013

DO - 10.1016/j.ijid.2024.02.013

M3 - Article

C2 - 38395221

SN - 1201-9712

VL - 142

JO - International journal of infectious diseases : IJID

JF - International journal of infectious diseases : IJID

M1 - 106970

ER -

Cerebrospinal fluid inflammatory markers to differentiate between neonatal bacterial meningitis and sepsis: a prospective study of diagnostic accuracy

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Keywords

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