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Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease

Abstract

Purpose

Invasive pneumococcal disease (IPD) is responsible for substantial mortality and morbidity worldwide. We aimed to identify host and bacterial factors associated with 30-day mortality in 18-year-old patients hospitalized with IPD in France from 2013 to 2015.

Methods

This study analyzed data collected from consecutives IPD cases included in two parallel multi-center cohort studies: COMBAT study (280 patients with pneumococcal community-acquired bacterial meningitis) and SIIP study (491 patients with non-meningitis IPD). Factors associated with 30-day mortality were identified using logistic regression.

Results

Among the 771 enrolled patients (median age 66 years, IQR [52.0–79.7]), 592/767 (77.2%) had at least one chronic disease. Patients with meningitis were younger (60.2 vs 70.9 years; p < 0.001) and had fewer chronic diseases than those with non-meningitis IPD (73.3% vs 79.4%; p = 0.05). Non-vaccine serotypes were more frequent in meningitis patients than in those with other IPD (36.1% vs 23.1%; p < 0.001). The overall 30-day mortality was 16.7% and patients with concurrent meningitis and extra-cerebral IPD had the highest 30-day mortality rate (26.5%). On multivariate analyses, older age, history of malignant solid tumor, meningeal IPD and serotypes previously identified with high mortality potential were independently associated with 30-day mortality. Of the serotypes with high mortality potential, 80% were included in licensed (PCV13 or PPV23) vaccines.

Conclusion

We observed an effect of both host factors and pneumococcal serotypes on 30-day mortality in IPD. This highlights the need for a focused strategy to vaccinate at-risk patients.

Clinical trial

ClinicalTrial. Gov identification number: NCT01730690

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Acknowledgements

Combat Study Group. Principal Investigator: Xavier Duval. Steering Committee: Bruno Hoen, Bruno Mourvillier, Marie-Cécile Ploy, Sarah Tubiana, Emmanuelle Varon. Scientific committee: steering committee and the following members François Caron, Pierre-Edouard Bollaert, Olivier Gaillot, Muhamed-Kheir Taha, Claire Poyart, Stephane Bonacorsi, François Vandenesch, Emmanuelle Cambau, Marc Lecuit, Alain Gravet, Bruno Frachet, Thomas Debroucker, Daniel Levy Bruhl, François Raffi, Marie Preau. Combat Clinical Centers: Nadia Anguel, Laurent Argaud, Sophie Arista, Laurence Armand-Lefevre, Stéphanie Balavoine, Régine Baraduc, Guilène Barnaud, Guillaume Beraud, Louis Bernard, Georges Bernars, Dominique Bertei, Emilie Bessede, Typhaine Billard Pomares, Charlotte Biron, Stéphane Bland, Julien Boileau, Patrice Boubeau, Sandra Bourdon, Aurore Bousquet, Sophie Boyer, Alexis Bozorg-Grayeli, Laurent Bret, Cédric Bretonniere, François Bricaire, Elsa Brocas, Michel Brun, Jennifer Buret, Christophe Burucoa, Jean Cabalion, Mathieu Cabon, Emmanuelle Cambau, Guillaume Camuset, Christophe Canevet, François Caron, Anne Carricajo, Bernard Castan, Eric Caumes, Charles Cazanave, Amélie Chabrol, Thibaut Challan-Belval, Vanessa Chanteperdrix-Marillier, Chantal Chaplain, Caroline Charlier-Woerther, Hélène Chaussade, Catherine Chirouze, Bernard Clair, Julien Colot, Jean-Marie Conil, Hugues Cordel, Philippe Cormier, Joël Cousson, Pierrick Cronier, Eric Cua, Anne Dao-Dubremetz, Sylvie Dargere, Nicolas Degand, Sophie Dekeyser, Deborah Delaune, Eric Denes, Pierre-Francois Dequin, Diane Descamps, Elodie Descloux, Jean-Luc Desmaretz, Jean-Luc Diehl, Jérôme Dimet, Aurélien Dinh, Xavier Duval, Lelia Escaut, Claude Fabe, Frédéric Faibis, Clara Flateau, Nathalie Fonsale, Emmanuel Forestier, Nicolas Fortineau, Amandine Gagneux-Brunon, Caroline Garandeau, Magali Garcia, Denis Garot, Stéphane Gaudry, François Goehringer, Alain Gravet, Valérie Gregoire-Faucher, Marine Grosset, Camélia Gubavu, Isabelle Gueit, Dominique Guelon, Thomas Guimard, Jérôme Guinard, Tahar Hadou, Jean-Pierre Helene, Sandrine Henard, Benoit Henry, Anne-Cécile Hochart, Bruno Hoen, Gabriela Illes, Sylvain Jaffuel, Irène Jarrin, Françoise Jaureguy, Cédric Joseph, Marie-Emmanuelle Juvin, Samer Kayal, Solen Kerneis, Isabelle Lamaury, Philippe Lanotte, Etienne Laurens, Henri Laurichesse, Cécile Le Brun, Vincent Le Moing, Paul Le Turnier, Hervé Lecuyer, Sylvie Ledru, Céline Legrix, Adrien Lemaignen, Chantal Lemble, Ludovic Lemee, Olivier Lesens, Marion Levast, Claire Lhommet, Silvija Males, Edith Malpote, Guillaume Martin-Blondel, Matthieu Marx, Raphael Masson, Olivier Matray, Aurore Mbadi, Frédéric Mechai, Guillaume Mellon, Audrey Merens, Marie Caroline Meyohas, Adrien Michon, Joy Mootien Yoganaden, David Morquin, Stéphane Mouly, Natacha Mrozek, Sophie Nguyen, Yohan Nguyen, Maja Ogielska, Eric Oziol, Bernard Page, Solène Patrat-Delon, Isabelle Patry, André Pechinot, Sandrine Picot, Denys Pierrejean, Lionel Piroth, Claire Plassart, Patrice Plessis, Marie-Cécile Ploy, Laurent Portel, Patrice Poubeau, Marie Poupard, Claire Poyart, Thierry Prazuck, Luc Quaesaet, François Raffi, Adriatsiferana Ramanantsoa, Christophe Rapp, Laurent Raskine, Josette Raymond, Matthieu Revest, Agnès Riche, Stéphanie Robaday-Voisin, Frédéric Robin, Jean-Pierre Romaszko, Florence Rousseau, Anne-Laure Roux, Cécile Royer, Matthieu Saada, Dominique Salmon, Carlo Saroufim, Jean Luc Schmit, Manuela Sebire, Christine Segonds, Valérie Sivadon-Tardy, Nathalie Soismier, Olivia Son, Simon Sunder, Florence Suy, Didier Tande, Jacques Tankovic, Nadia Valin, Nicolas Van Grunderbeeck, François Vandenesch, Emmanuelle Varon, Renaud Verdon, Michel Vergnaud, Véronique Vernet-Garnier, Magali Vidal, Virginie Vitrat, Daniel Vittecoq, Fanny Vuotto. Coordination and statistical analyses (Clinical trial unit, Hôpitaux Universitaires Paris Nord Val de Seine, AP-HP, Paris) : Isabelle Gorenne, Cédric Laouenan, Estelle Marcault, France Mentre, Blandine Pasquet, Carine Roy, Sarah Tubiana. Scientific partnership: SPLIF, CMIT, SRLF, SFM, REIVAC, SFORL, APNET, SPF. Partners: ORP (Marie-Cécile PLOY), GPIP/ACTIV (Corinne Levy). Sponsor: DRCI APHP, Flore Lacassin. SIIP Study Group. Philippe Arsac, Martha Benoit, Louis Bernard, François Bissuel, Laurent Bret, Natalie Brieu, Jennifer Burret, Claudia Carvalhoschneider, Hélène Champagne, Joséphine Chapalain, Hubert Chardon, Pascal Chavanet, Judith Ducruet, Olivier Epaulard, Marc Fabre, Dominique Fasquelle, Emmanuel Forestier, Jean-Marc Galempoix, Guillaume Gautier, Claire Goulard De Curraize, Alain Gracet, Camélia Gubavu, Jerome Guinard, Tarik Habet, Aurélie Haudour, Caroline Henry, Cécile Hombrouckalet, Céline Janssen, Jean-Paul Kisteman, Philippe Lanotte, Marie-Frédérique Lartigue, Claire Launois, Cécile Lebrun, Laurence Legout, Marion Levast, Yannick Madoux, Laurence Maulin, Stéphanie Mestrallet, Abdo Mohareb, Joy Mootien, Yohan Nguyen, Franck Noel, Maja Ogielska, Agathe Ogier Desserrey, Anne Paleau, Simona Pavel, André Pechinot, Isabelle Pelloux, Camille Petillon, Hélène Petitprez, Bianca Podac, Jerome Poirot, Bénédicte Ponceau, Nathalie Prieur, Christine Recule, Orlando Saraceni, Jacques Sartre, Farid Sifaoui, Catherine Simonin, Christophe Strady, Charlotte Tellini, Anthony Texier, Maxime Thouvenin, Anne Tixier, Pauline Tremeaux, Pascale Verger, Véronique Vernet-Garnier, Jean-Pierre Verquin, Virginie Vitrat, Isabelle Vray, Oana Zamfir, Laure Zucchini.

Funding

The COMBAT study was supported by the Assistance Publique Hopitaux de Paris, French Ministry of Health, Inserm, SPILF, and the Pfizer Pharmaceutical company, which also funded ORP. The study was endorsed by the following professional organizations: Association Pour l’enseignement de la Thérapeutique, Société de Pathologie Infectieuse de Langue Française, Société Française de Microbiologie, Société Nationale Française de Médecine Interne, Société de Réanimation de Langue Française, Société Française de Gérontologie, Société Française d’Anesthésie-Réanimation. The SIIP study was supported by (i) the Société de Pathologie Infectieuse de Langue Fran.aise (SPILF; the French Infectious Diseases Society), (ii) Santé Publique France (SpFrance; the French National Public Health Agency), (iii) the European Centre for Disease Prevention and Control (ECDC), and (iv) Pfizer. The Regional Observatories of Pneumococci (Observatoires Régionaux du Pneumocoque) were supported by Pfizer, BioMerieux, and Sanofi.

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Correspondence to Xavier Duval.

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The members of “COMBAT and SIIP Study Groups” are presented in the Acknowledgements section.

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Benadji, A., Duval, X., Danis, K. et al. Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease. Infection (2021). https://doi.org/10.1007/s15010-021-01688-5

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Keywords

  • Invasive pneumococcal disease
  • Streptococcus pneumoniae
  • 30-day mortality
  • Pneumococcal vaccine