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Long-term neuro-functional disability in adult patients with community-acquired bacterial meningitis

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Abstract

Purpose

To investigate the prevalence of neuro-functional disability and its determinants 12 months after community-acquired bacterial meningitis (CABM) in adult patients.

Methods

In a prospective multicenter cohort study (COMBAT), all consecutive cases of CABM were enrolled and followed up for 12 months. Neuro-functional disability at 12 months was evaluated using a combination of the Glasgow Outcome Scale (functional disability), and the modified Rankin Disability Scale (physical disability). Factors associated with neuro-functional disability were identified by multivariate logistic regression.

Results

Among 281 patients, 84 (29.9%) patients exhibited neuro-functional disability at 12 months: 79 (28.1%) with functional disability and 51 (18.1%) with physical disability. Overall, 6 patients (2.1%) died during the follow-up. The most common pathogen identified was Streptococcus pneumoniae (131/272, 48.2%); 77/268 patients (28.7%) had a physical disability at hospital discharge. Factors independently associated with 12-month neuro-functional disability were a pneumococcal meningitis (adjusted OR = 2.8; 95% confidence interval (CI) = [1.3; 6.7]), the presence of a physical disability at hospital discharge (aOR = 2.3; 95%CI = [1.2; 4.4]) and the presence of behavioral disorders at hospital-discharge (aOR = 5.9; 95%CI = [1.6; 28.4]). Dexamethasone use was not significantly associated with neuro-functional disability (OR = 0.2; 95%CI = [< 0.1;1.3]).

Conclusion

Neuro-functional disability is frequently reported 12 months after CABM. Detailed neurological examination at discharge is needed to improve the follow-up.

Trial registration

NCT01730690.

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Availability of data and material

Data will be made upon reasonable request to the corresponding author.

Code availability

Not applicable.

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Acknowledgements

Combat study group; Principal investigator: X. Duval. Steering Committee: B. Hoen, B. Mourvillier, E. Varon, S. Tubiana, M. C. Ploy. Scientific committee: steering committee and the following members F. Caron, Pe. Bollaert, O. Gaillot, Mk. Taha, C. Poyart, S Bonacorsi, F. Vandenesch, E. Cambau, M Lecuit, A. Gravet, B. Frachet, T. Dde Broucker, D. Levy Bruhl, F. Raffi. Clinical centers: B. Abraham, F. Ader, E. Ancel, N. Anguel, L. Argaud, S. Arista, L. Armand-Lefevre, MN. Bachelier, S. Balavoine, R. Baraduc, G. Barnaud, G. Beraud, D. Bertei, E. Bessede, T. Billard Pomares, C. Biron, G. Blanchard-Marche, S. Bland, J. Boileau, C. Bornstain, S. Bourdon, A. Bousquet, S. Boyer, A. Bozorg-Grayeli, L. Bret, F. Bricaire, E. Brocas, M. Brun, J. Buret, C. Burucoa, E. Cambau, G. Camuset, C. Canevet, F. Caron, A. Carricajo, I. Casin, D. Cassignard, B. Castan, C. Cazanave, T. Challan-Belval, C. Chandesris, V. Chanteperdrix-Marillier, C. Chaplain, C. Charlier-Woerther, H. Chaussade, C. Chirouze, M. Chomarat, YE Claessens, B. Clair, D. Combaux, JM Conil, H. Cordel, P. Cormier, J. Cousson, P. Cronier, E. Cua, V. Daneluzzi, A. Dao Dubremetz, A. Defarcy, N. Degand, S. Dekeyser, D. Delaune, E. Denes, D. Descamps, Jl Desmaretz, E. Devaud, MC. Di Palma, S. Diamantis, JL. Diehl, J. Dimet, A. Dinh, X. Duval, E. Descloux, J. Colot, A. Emirian, O. Epaulard, L. Escaut, C. Fabe, T. Ferry, H. Fiette, C. Flateau, N. Fonsale, E. Forestier, N. Fortineau, T. Fraisse, F. Faibis, M. Froidure, S. Gabriel-Solean, A. Gagneux-Brunon, Garandeau, M. Garcia, V. Garnier, S. Gaudry, R. Ghozzi, A. Gravet, V. Gregoire-Faucher, M. Grosset, I. Gueit, D. Guelon, C. Guillet Caruba, T. Guimard, Y. Guimard, J. Guinard, T Hadou, JP. Helene, S. Henard, B. Henry, R. Hernu, AC. Hochart, B. Hoen, N. Idri, G. Illes, X. Jacob, S. Jaffuel, D. Jan, I. Jarrin, F. Jaureguy, C. Joseph, ME. Juvin, S. Kayal, F. Lacassin, M. Lafaurie, B. Lalanne, I. Lamaury, P. Lanotte, MF. Lartigue, Y. Latorre, P. Laudat, E. Laurens, H. Laurichesse, C. Le Brun, V. Le Moing, P. Le Turnier, H. Lecuyer, S. Ledru, L. Legout, C. Legrix, A. Lemaignen, C. Lemble, L. Lemee, S. Leotard, O. Lesens, P. Lesprit, M. Levast, F. Louis, L. Quaesaet, N. Luizy, S. Males, E. Malpote, G. Martin-Blondel, V. Martinez, R. Masson, O. Matray, A. Mbadi, F. Mechai, A. Merens, MC. Meyohas, G. Michel, A. Michon, J. Mootien Yoganaden, D. Morquin, S. Mouly, N. Mrozek, S. Nguyen, Y. Nguyen, A. Odinotte, M. Ogielska, E. Oziol, B. Page, E. Parisi-Duchene, T. Pasdeloup, S. Patrat-Delon, I. Patry, A. Pechinot, I. Pelloux, S. Picot, J. Pierre, L. Piroth, C. Plassart, P. Plessis, C. Ploton, MC. Ploy, L. Portel, M. Poupard, C. Poyart, T. Prazuck, F. Raffi, A. Ramanantsoa, C. Rapp, L. Raskine, J. Raymond, M. Revest, A. Riche, S. Robaday-Voisin, F. Robin, F. Roblot, JP. Romaszko, F. Rousseau, AL. Roux, C. Royer, M. Saada, D. Salmon, C. Saroufim, JL. Schmit, M. Sebire, C. Segonds, F. Sifaoui, V. Sivadon-Tardy, N. Soismier, K. Solen, A. Sommabere, O. Son, JP. Stahl, R. Steux, S. Sunder, F. Suy, D. Tande, J. Tankovic, S. Tigaud, B. Tourrand, N. Valin, N. Van Grunderbeeck, F. Vandenesch, E. Varon, R. Vatan, C. Venot, M. Vergnaud, Vernet, M. Vidal, V. Vitrat, D. Vittecoq, F. Vuotto, A. Chabrol, J. Cabalion. Coordination and statistical analyses (Clinical trial unit, Hôpitaux Universitaires Paris Nord Val de Seine, AP-HP, Paris): GORENNE Isabelle, LAOUENAN Cédric, MARCAULT Estelle, MENTRE France, PASQUET Blandine, ROY Carine, TUBIANA Sarah F. Mentré, C. Laouenan, I. Gorenne, E. Marcault, P. Manchon, B. Pasquet, C. Roy. Scientific partnership: SPLIF, CMIT, SRLF, SFM, REIVAC, SFORL, APNET. Partners: ORP (MC PLOY), GPIP/ACTIV (Corinne Levy). Fundings: French ministry of health, Inserm, SPILF, Pfizer pharmaceutical company. Sponsor: DRCI APHP. ClinicalTrial.gov identification number: NCT01730690.

X. Duval, B. Hoen, B. Mourvillier, E. Varon, S. Tubiana, M. C. Ploy, F. Caron, Pe. Bollaert, O. Gaillot, Mk. Taha, C. Poyart, S Bonacorsi, F. Vandenesch, E. Cambau, M. Lecuit, A. Gravet, B. Frachet, T. De Broucker, D. Levy Bruhl, F. Raffi, B. Abraham, F. Ader, E. Ancel, N. Anguel, L. Argaud, S. Arista, L. Armand-Lefevre, M. N. Bachelier, S. Balavoine, R. Baraduc, G. Barnaud, G. Beraud, D. Bertei, E. Bessede, T. Billard Pomares, C. Biron, G. Blanchard-Marche, S. Bland, J. Boileau, C. Bornstain, S. Bourdon, A. Bousquet, S. Boyer, A. Bozorg-Grayeli, L. Bret, F. Bricaire, E. Brocas, M. Brun, J. Buret, C. Burucoa, E. Cambau, G. Camuset, C. Canevet, F. Caron, A. Carricajo, I. Casin, D. Cassignard, B. Castan, C. Cazanave, T. Challan-Belval, C. Chandesris, V. Chanteperdrix-Marillier, C. Chaplain, C. Charlier-Woerther, H. Chaussade, C. Chirouze, M. Chomarat, Y. E. Claessens, B. Clair, D. Combaux, J. M. Conil, H. Cordel, P. Cormier, J. Cousson, P. Cronier, E. Cua, V. Daneluzzi, A. Dao Dubremetz, A. Defarcy, N. Degand, S. Dekeyser, D. Delaune, E. Denes, D. Descamps, Jl. Desmaretz, E. Devaud, M. C. Di Palma, S. Diamantis, J. L. Diehl, J. Dimet, A. Dinh, X. Duval, E. Descloux, J. Colot, A. Emirian, O. Epaulard, L. Escaut, C. Fabe, T. Ferry, H. Fiette, C. Flateau, N. Fonsale, E. Forestier, N. Fortineau, T. Fraisse, F. Faibis, M. Froidure, S. Gabriel-Solean, A. Gagneux-Brunon, Garandeau, M. Garcia, V. Garnier, S. Gaudry, R. Ghozzi, A. Gravet, V. Gregoire-Faucher, M. Grosset, I. Gueit, D. Guelon, C. Guillet Caruba, T. Guimard, Y. Guimard, J. Guinard, T Hadou, J. P. Helene, S. Henard, B. Henry, R. Hernu, A. C. Hochart, B. Hoen, N. Idri, G. Illes, X. Jacob, S. Jaffuel, D. Jan, I. Jarrin, F. Jaureguy, C. Joseph, M. E. Juvin, S. Kayal, F. Lacassin, M. Lafaurie, B. Lalanne, I. Lamaury, P. Lanotte, M. F. Lartigue, Y. Latorre, P. Laudat, E. Laurens, H. Laurichesse, C. Le Brun, V. Le Moing, P. Le Turnier, H. Lecuyer, S. Ledru, L. Legout, C. Legrix, A. Lemaignen, C. Lemble, L. Lemee, S. Leotard, O. Lesens, P. Lesprit, M. Levast, F. Louis, L. Quaesaet, N. Luizy, S. Males, E. Malpote, G. Martin-Blondel, V. Martinez, R. Masson, O. Matray, A. Mbadi, F. Mechai, A. Merens, M. C. Meyohas, G. Michel, A. Michon, J. Mootien Yoganaden, D. Morquin, S. Mouly, N. Mrozek, S. Nguyen, Y. Nguyen, A. Odinotte, M. Ogielska, E. Oziol, B. Page, E. Parisi-Duchene, T. Pasdeloup, S. Patrat-Delon, I. Patry, A. Pechinot, I. Pelloux, S. Picot, J. Pierre, L. Piroth, C. Plassart, P. Plessis, C. Ploton, M. C. Ploy, L. Portel, M. Poupard, C. Poyart, T. Prazuck, F. Raffi, A. Ramanantsoa, C. Rapp, L. Raskine, J. Raymond, M. Revest, A. Riche, S. Robaday-Voisin, F. Robin, F. Roblot, J. P. Romaszko, F. Rousseau, A. L. Roux, C. Royer, M. Saada, D. Salmon, C. Saroufim, J. L. Schmit, M. Sebire, C. Segonds, F. Sifaoui, V. Sivadon-Tardy, N. Soismier, K. Solen, A. Sommabere, O. Son, JP. Stahl, R. Steux, S. Sunder, F. Suy, D. Tande, J. Tankovic, S. Tigaud, B. Tourrand, N. Valin, N. Van Grunderbeeck, F. Vandenesch, E. Varon, R. Vatan, C. Venot, M. Vergnaud, Vernet, M. Vidal, V. Vitrat, D. Vittecoq, F. Vuotto, A. Chabrol, J. Cabalion, S. Tubiana, F. Mentré, C. Laouénan, I. Gorenne, E. Marcault, P. Manchon, B. Pasquet, C. Roy

Funding

The cohort was funded by the French ministry of health, APHP DRCI, Inserm, French society of infectious diseases, and Pfizer pharmaceutical company.

Author information

Authors and Affiliations

  1. Centre d’Investigation Clinique, Hôpital Bichat Claude Bernard, AP-HP, Hôpital Bichat, Inserm CIC 1425, 46, rue Henri Huchard, 75018, Paris, France

    Souade Akroum, Sarah Tubiana, Xavier Duval & Charles Burdet

  2. Université Paris Cité, IAME, INSERM, 75018, Paris, France

    Sarah Tubiana, Xavier Duval & Charles Burdet

  3. Centre de Ressources Biologiques, AP-HP, Hôpital Bichat, 75018, Paris, France

    Sarah Tubiana

  4. Service de Neurologie, Hôpital Delafontaine, 93200, Saint-Denis, France

    Thomas de Broucker

  5. Service de maladies infectieuses et tropicales, dermatologie, médecine interne, Centre Hospitalier Universitaire de Pointe-à-Pitre, 97159, Pointe-à-Pitre, France

    Nathalie Dournon

  6. Centre Hospitalier Intercommunal de Créteil, Centre National de Référence des Pneumocoques, 94010, Créteil, France

    Emmanuelle Varon

  7. Centre Hospitalier Universitaire de Limoges, Observatoire Régional des Pneumocoques, 87000, Limoges, France

    Marie Cécile Ploy

  8. Service de Médecine Intensive et Réanimation Polyvalente, CHU Reims, 51100, Reims, France

    Bruno Mourvillier

  9. Service de Médecine Interne, Centre Hospitalier de Béziers, 34500, Béziers, France

    Eric Oziol

  10. Service de Médecine Interne, Centre Hospitalier Territorial de Nouméa, 98849, Nouméa, France

    Flore Lacassin

  11. Service de Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Clermont-Ferrand, 63003, Clermont-Ferrand, France

    Henri Laurichesse

  12. Service de Maladies Infectieuses et Tropicales, CHU de Nancy, Hôpitaux de Brabois, 54511, Vandoeuvre-lès-Nancy, France

    Bruno Hoen

  13. Département d’Epidémiologie, Biostatistique et Recherche, AP-HP, Hôpital Bichat, 75018, Paris, France

    Charles Burdet

Authors
  1. Souade Akroum
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  2. Sarah Tubiana
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  3. Thomas de Broucker
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  4. Nathalie Dournon
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  5. Emmanuelle Varon
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  6. Marie Cécile Ploy
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  7. Bruno Mourvillier
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  8. Eric Oziol
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  9. Flore Lacassin
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  10. Henri Laurichesse
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  11. Bruno Hoen
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  12. Xavier Duval
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  13. Charles Burdet
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Consortia

and the COMBAT study group

  • X Duval
  • , B Hoen
  • , B Mourvillier
  • , E Varon
  • , S Tubiana
  • , M. C. Ploy
  • , F Caron
  • , Pe. Bollaert
  • , O Gaillot
  • , Mk. Taha
  • , C Poyart
  • , S Bonacorsi
  • , F Vandenesch
  • , E Cambau
  • , M Lecuit
  • , A Gravet
  • , B Frachet
  • , T De Broucker
  • , D Levy Bruhl
  • , F Raffi
  • , B Abraham
  • , F Ader
  • , E Ancel
  • , N Anguel
  • , L Argaud
  • , S Arista
  • , L Armand-Lefevre
  • , M. N. Bachelier
  • , S Balavoine
  • , R Baraduc
  • , G Barnaud
  • , G Beraud
  • , D Bertei
  • , E Bessede
  • , T Billard Pomares
  • , C Biron
  • , G Blanchard-Marche
  • , S Bland
  • , J Boileau
  • , C Bornstain
  • , S Bourdon
  • , A Bousquet
  • , S Boyer
  • , A Bozorg-Grayeli
  • , L Bret
  • , F Bricaire
  • , E Brocas
  • , M Brun
  • , J Buret
  • , C Burucoa
  • , E Cambau
  • , G Camuset
  • , C Canevet
  • , F Caron
  • , A Carricajo
  • , I Casin
  • , D Cassignard
  • , B Castan
  • , C Cazanave
  • , T Challan-Belval
  • , C Chandesris
  • , V Chanteperdrix-Marillier
  • , C Chaplain
  • , C Charlier-Woerther
  • , H Chaussade
  • , C Chirouze
  • , M Chomarat
  • , Y. E. Claessens
  • , B Clair
  • , D Combaux
  • , J. M. Conil
  • , H Cordel
  • , P Cormier
  • , J Cousson
  • , P Cronier
  • , E Cua
  • , V Daneluzzi
  • , A Dao Dubremetz
  • , A Defarcy
  • , N Degand
  • , S Dekeyser
  • , D Delaune
  • , E Denes
  • , D Descamps
  • , J. l. Desmaretz
  • , E Devaud
  • , M. C. Di Palma
  • , S Diamantis
  • , J. L. Diehl
  • , J Dimet
  • , A Dinh
  • , X Duval
  • , E Descloux
  • , J Colot
  • , A Emirian
  • , O Epaulard
  • , L Escaut
  • , C Fabe
  • , T Ferry
  • , H Fiette
  • , C Flateau
  • , N Fonsale
  • , E Forestier
  • , N Fortineau
  • , T Fraisse
  • , F Faibis
  • , M Froidure
  • , S Gabriel-Solean
  • , A Gagneux-Brunon
  • ,  Garandeau
  • , M Garcia
  • , V Garnier
  • , S Gaudry
  • , R Ghozzi
  • , A Gravet
  • , V Gregoire-Faucher
  • , M Grosset
  • , I Gueit
  • , D Guelon
  • , C Guillet Caruba
  • , T Guimard
  • , Y Guimard
  • , J Guinard
  • , T Hadou
  • , J. P. Helene
  • , S Henard
  • , B Henry
  • , R Hernu
  • , A. C. Hochart
  • , B Hoen
  • , N Idri
  • , G Illes
  • , X Jacob
  • , S Jaffuel
  • , D Jan
  • , I Jarrin
  • , F Jaureguy
  • , C Joseph
  • , M. E. Juvin
  • , S Kayal
  • , F Lacassin
  • , M Lafaurie
  • , B Lalanne
  • , I Lamaury
  • , P Lanotte
  • , M. F. Lartigue
  • , Y Latorre
  • , P Laudat
  • , E Laurens
  • , H Laurichesse
  • , C Le Brun
  • , V Le Moing
  • , P Le Turnier
  • , H Lecuyer
  • , S Ledru
  • , L Legout
  • , C Legrix
  • , A Lemaignen
  • , C Lemble
  • , L Lemee
  • , S Leotard
  • , O Lesens
  • , P Lesprit
  • , M Levast
  • , F Louis
  • , L Quaesaet
  • , N Luizy
  • , S Males
  • , E Malpote
  • , G Martin-Blondel
  • , V Martinez
  • , R Masson
  • , O Matray
  • , A Mbadi
  • , F Mechai
  • , A Merens
  • , M. C. Meyohas
  • , G Michel
  • , A Michon
  • , J Mootien Yoganaden
  • , D Morquin
  • , S Mouly
  • , N Mrozek
  • , S Nguyen
  • , Y Nguyen
  • , A Odinotte
  • , M Ogielska
  • , E Oziol
  • , B Page
  • , E Parisi-Duchene
  • , T Pasdeloup
  • , S Patrat-Delon
  • , I Patry
  • , A Pechinot
  • , I Pelloux
  • , S Picot
  • , J Pierre
  • , L Piroth
  • , C Plassart
  • , P Plessis
  • , C Ploton
  • , M . C. Ploy
  • , L Portel
  • , M Poupard
  • , C Poyart
  • , T Prazuck
  • , F Raffi
  • , A Ramanantsoa
  • , C Rapp
  • , L Raskine
  • , J Raymond
  • , M Revest
  • , A Riche
  • , S Robaday-Voisin
  • , F Robin
  • , F Roblot
  • , J. P. Romaszko
  • , F Rousseau
  • , A . L. Roux
  • , C Royer
  • , M Saada
  • , D Salmon
  • , C Saroufim
  • , J . L. Schmit
  • , M Sebire
  • , C Segonds
  • , F Sifaoui
  • , V Sivadon-Tardy
  • , N Soismier
  • , K Solen
  • , A Sommabere
  • , O Son
  • , JP Stahl
  • , R Steux
  • , S Sunder
  • , F Suy
  • , D Tande
  • , J Tankovic
  • , S Tigaud
  • , B Tourrand
  • , N Valin
  • , N Van Grunderbeeck
  • , F Vandenesch
  • , E Varon
  • , R Vatan
  • , C Venot
  • , M Vergnaud
  • ,  Vernet
  • , M Vidal
  • , V Vitrat
  • , D Vittecoq
  • , F Vuotto
  • , A Chabrol
  • , J Cabalion
  • , Isabelle Gorenne
  • , Cédric Laouenan
  • , Estelle Marcault
  • , France Mentre
  • , Blandine Pasquet
  • , Carine Roy
  • , Sarah F Mentré Tubiana
  • , C Laouenan
  • , I Gorenne
  • , E Marcault
  • , P Manchon
  • , B Pasquet
  •  & C Roy

Corresponding author

Correspondence to Xavier Duval.

Ethics declarations

Conflict of interest

We have read and understood the Infection policy on declaration of interests and have no relevant interests to declare.

Ethics approval

The study was approved by the institutional Ethics Committee Ile-de-France 4 (IRB #00003835, approval #2012-16NI) and by the French Data Protection Authority (approval ECY/FLR/AR128794).

Consent to participate

All participants provided consent to participate before entering the study.

Consent for publication

Not applicable.

Additional information

The members of the COMBAT study group are mentioned in Acknowledgements section.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 30 KB)

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Akroum, S., Tubiana, S., de Broucker, T. et al. Long-term neuro-functional disability in adult patients with community-acquired bacterial meningitis. Infection 50, 1363–1372 (2022). https://doi.org/10.1007/s15010-022-01855-2

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  • DOI: https://doi.org/10.1007/s15010-022-01855-2

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