Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Salas, Antonio; Carrol, Enitan D.; Levin, Michael; Coin, Lachlan; Gormley, Stuart; Hamilton, Shea; Herberg, Jethro; Hourmat, Bernardo; Hoggart, Clive; Kaforou, Myrsini; Sancho‐Shimizu, Vanessa; Wright, Victoria; Abdulla, Amina; Agapow, Paul; Bartlett, Maeve; Bellos, Evangelos; Eleftherohorinou, Hariklia; Galassini, Rachel; Inwald, David; Mashbat, Meg; Menikou, Stefanie; Mustafa, Sobia; Nadel, Simon; Rahman, Rahmeen; Thakker, Clare; Bokhandi, S; Power, Sue; Barham, Heather; Pathan, Nazima; Ridout, Jenna; White, Deborah; Thurston, Sarah; Faust, Saul N; Patel, Sanjay; McCorkell, Jenni; Davies, Patrick; Crate, Lindsey; Navarra, Helen; Carter, Stephanie; Ramaiah, R; Patel, Rekha; Tuffrey, Catherine; Gribbin, Andrew; McCready, S.; Peters, Mark; Hardy, Katie; Standing, Fran; O'Neill, Lauren; Abelake, Eugenia; Deep, Akash; Nsirim, Eniola; Pollard, Andrew J.; Willis, Louise; Young, Zoë; Royad, C; White, Sonia; Fortune, Peter Marc; Hudnott, Phil; Martinón-Torres, Federico; Ellacuriaga, Antonio Salas; González, Fernando Álvez; Barral-Arca, Ruth; Cebey-López, Miriam; Currás-Tuala, María José; García, Natalia; Vicente, Luisa García; Gómez-Carballa, Alberto; Gómez-Rial, José; Beiroa, Andrea Grela; Grande, Antonio Justicia; Iglesias, Pilar Leboráns; Santos, Alba Elena Martínez; Martinón-Torres, Nazareth; Sánchez, José María Martinón; Gutiérrez, Beatriz Morillo; Pérez, Belén Mosquera; Pacheco, Pablo Obando; Pardo-Seco, Jacobo; Pischedda, Sara; Rivero‐Calle, Irene; Rodrı́guez-Tenreiro, Carmen; Redondo-Collazo, Lorenzo; Fernández, Sonia Serén; Silva, María del Sol Porto; Vega, Ana; Trillo, Lucía Vilanova; Reyes, Susana Beatriz; León, María Cruz León; Mingorance, Álvaro Navarro; Barrios, Xavier Gabaldó; Vergara, E. Oñate; Concha-Torre, Andrés; Vivanco, Ana; Fernández, Reyes; Sánchez, F. Giménez; Forte, Miguel; Rojo, Pablo; Contreras, Jesús Ruíz; Palacios, Alba; Ibarrondo, Cristina Epalza; Fernández-Cooke, Elisa; Navarro, Marisa; Álvarez, Cristina Álvarez; Lozano, María José; Carreras, Eduardo; Sanagustín, Sonia Brió; Neth, Olaf; Padilla, María del Carmen Martínez; Tato, Luis Manuel Prieto; Guillén, Sara; Silveira, Laura Fernández; Moreno, David; Groot, Ronald de; Furth, A. Marceline van; Flier, Michiel van der; Boeddha, Navin P.; Driessen, Gertjan J.; Hazelzet, Jan A.; Kuijpers, Taco W.; Pajkrt, Dasja; Sanders, Elisabeth A. M.; Beek, Diederik van de; Ende, Arie van der; Philipsen, Ria; Adeel, A. O. A.; Breukels, M. A.; Brinkman, D. M. C.; Korte, Carla CMM de; Vries, Esther de; Waal, Wouter J. de; Dekkers, Roel; Dings-Lammertink, Anouk; Doedens, Rienus A.; Donker, Albertine E.; Dousma, Mieke; Faber, Tina E; Gerrits, G. P. J. M.; Gerver, J.A.M.; Heidema, Jojanneke; Veen, J. Homan-van der; Jacobs, Monique; Jansen, Nicolaas J.; Kawczyński, Paweł; Klucovska, K.; Kneyber, Martin C. J.; Koopman-Keemink, Y.; Langenhorst, Veerle; Leusink, J.; Loza, Bettina F.; Merth, I. T.; Miedema, Carien J.; Neeleman, C.; Noordzij, Jeroen G.; Obihara, C C; Gils, A. L. T. van Overbeek - van; Poortman, Geriska H; Potgieter, S. T.; Potjewijd, Joke; Rosias, Philippe; Sprong, Tom; Tussher, G. W. ten; Thio, Boony J.; Tramper-Stranders, Gerdien A; Deuren, Marcel van; Meer, H. van der; Kuppevelt, Andre JM van; Wermeskerken, Anne-Marie van; Verwijs, W. A.; Wolfs, Tom F. W.; Schlapbach, Luregn J.; Agyeman, Philipp; Aebi, Christoph; Giannoni, Éric; Stocker, Martin; Posfay‐Barbe, Klara M.; Heininger, Ulrich; Bernhard-Stirnemann, Sara; Niederer-Loher, Anita; Kahlert, Christian R.; Hasters, Paul; Relly, Christa; Baer, Walter; Berger, Christoph; Carrol, Enitan D.; Paulus, Stéphane; Frederick, Hannah; Jennings, Rebecca; Johnston, Joanne; Kenwright, Rhian; Fink, Colin G.; Pinnock, Elli; Emonts, Marieke; Agbeko, Rachel; Anderson, Suzanne T.; Secka, Fatou; Bojang, Kalifa; Sarr, Isatou; Kebbeh, Ngange; Sey, Gibbi; Saidykhan, Momodou; Cole, Fatoumata; Thomas, Gilleh; Antonio, Martín; Zenz, Werner; Klobassa, Daniela S.; Binder, A.; Schweintzger, Nina A.; Sagmeister, Manfred G.; Baumgart, Hinrich; Baumgartner, Markus R.; Behrends, Uta; Biebl, Ariane; Birnbacher, Robert; Blanke, Jan-Gerd; Boelke, Carsten; Breuling, Kai; Brunner, Jürgen; Buller, Maria; Dahlem, Peter; Dietrich, Beate; Eber, Ernst; Elias, Johannes; Emhofer, Josef; Etschmaier, Rosa; Farr, Sebastian; Girtler, Ylenia; Grigorow, Irina; Heimann, Konrad; Ihm, Ulrike; Jaros, Zdenek; Kalhoff, Hermann; Kaulfersch, W; Kemen, Christoph; Klocker, Nina; Köster, Bernhard; Kohlmaier, Benno; Komini, Eleni; Kramer, Lydia; Neubert, Antje; Ortner, Daniel; Pescollderungg, Lydia; Pfurtscheller, Klaus; Reiter, Karl; Ristić, Goran S.; Rödl, Siegfried; Sellner, Andrea; Sonnleitner, Astrid; Sperl, Matthias; Stelzl, Wolfgang; Till, Holger; Trobisch, Andreas; Vierzig, Anne; Vogel, Ulrich; Weingarten, Christina; Welke, Stefanie; Wimmer, Andreas; Wintergerst, Uwe; Wüller, Daniel; Zaunschirm, Andrew; Ziuraite, Ieva; Žukovskaja, Veslava

doi:10.1016/s2352-4642(18)30113-5

Cited by 65 publications

(47 citation statements)

References 29 publications

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“…Future multicenter studies in larger populations are needed to draw firmer conclusions. In children with (suspected) bacterial infections presenting to the ED, mortality ranges from 0 to 2.2% and PICU transfer from 5.7 to 42% ( 22 , 27 – 29 ). In our cohort, mortality (0.7%) and PICU transfer (2.1%) was lower.…”

Section: Discussionmentioning

confidence: 99%

Translating Sepsis-3 Criteria in Children: Prognostic Accuracy of Age-Adjusted Quick SOFA Score in Children Visiting the Emergency Department With Suspected Bacterial Infection

et al. 2018

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Background: Recent attempts to translate Sepsis-3 criteria to children have been restricted to PICU patients and did not target children in emergency departments (ED). We assessed the prognostic accuracy of the age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) and compared the performance to SIRS and the quick Pediatric Logistic Organ Dysfunction-2 score (qPELOD-2). We studied whether the addition of lactate (qSOFA-L) would increase prognostic accuracy.Methods: Non-academic, single-center, retrospective study in children visiting the ED and admitted with suspected bacterial infection between March 2013 and January 2018. We defined suspected bacterial infection as initiation of antibiotic therapy within 24 h after ED entry. Age-adjusted qSOFA, SIRS, qPELOD-2, and qSOFA-L scores were compared by area under the receiver operating characteristics curve (AUROC) analysis. Primary outcome measure was PICU transfer and/or mortality and secondary outcome was prolonged hospital length of stay.Results: We included 864 ED visits [474 (55%) male; median age 2.5 years; IQR 9 months-6 years], of which 18 were transferred to a PICU and 6 ended in death [composite outcome PICU transfer and/or mortality; 23 admissions (2.7%)]. 179 (22.2%) admissions resulted in prolonged hospital length of stay. PICU transfer and/or death was present in 22.5% of visits with qSOFA≥2 (n = 40) compared to 2.0% of visits with qSOFA<2 (n = 444) (p < 0.01). qSOFA tends to be the best predictor of PICU transfer and/or mortality (AUROC 0.72 (95% CI, 0.57–0.86) compared to SIRS [0.64 (95% CI, 0.53–0.74), p = 0.23] and qPELOD-2 [0.60 (95% CI, 0.45–0.76), p = 0.03)]. Prolonged hospital length of stay was poorly predicted by qSOFA (AUROC 0.53, 95% CI 0.46–0.59), SIRS (0.49, 95% CI 0.44–0.54), and qPELOD-2 (0.51, 95%CI 0.45–0.57). qSOFA-L resulted in an AUROC of 0.67 (95% CI, 0.50–0.84) for PICU transfer and/or mortality and an AUROC of 0.56 (95% CI, 0.46–0.67) for prolonged hospital length of stay.Conclusion: The currently proposed bedside risk-stratification tool of Sepsis-3 criteria, qSOFA, shows moderate prognostic accuracy for PICU transfer and/or mortality in children visiting the ED with suspected bacterial infection. The addition of lactate did not improve prognostic accuracy. Future prospective studies in larger ED populations are needed to further determine the utility of the qSOFA score.

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Section: Discussionmentioning

confidence: 99%

Translating Sepsis-3 Criteria in Children: Prognostic Accuracy of Age-Adjusted Quick SOFA Score in Children Visiting the Emergency Department With Suspected Bacterial Infection

et al. 2018

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“…This may be a consequence of the inclusion criteria being too lax in the context of an increasingly immunised population. A recent Europe-wide study demonstrated that the disease burden of severe childhood infection is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections 31. However, in the UK, the childhood vaccination programme has resulted in massive reductions in the incidence of both group B meningococcal disease32 and invasive pneumococcal disease 33.…”

Section: Discussionmentioning

confidence: 99%

Restricted fluid bolus volume in early septic shock: results of the Fluids in Shock pilot trial

et al. 2018

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ObjectiveTo determine the feasibility of Fluids in Shock, a randomised controlled trial (RCT) of restricted fluid bolus volume (10 mL/kg) versus recommended practice (20 mL/kg).DesignNine-month pilot RCT with embedded mixed-method perspectives study.Setting13 hospitals in England.PatientsChildren presenting to emergency departments with suspected infection and shock after 20 mL/kg fluid.InterventionsPatients were randomly allocated (1:1) to further 10 or 20 mL/kg fluid boluses every 15 min for up to 4 hours if still in shock.Main outcome measuresThese were based on progression criteria, including recruitment and retention, protocol adherence, separation, potential trial outcome measures, and parent and staff perspectives.ResultsSeventy-five participants were randomised; two were withdrawn. 23 (59%) of 39 in the 10 mL/kg arm and 25 (74%) of 34 in the 20 mL/kg arm required a single trial bolus before the shock resolved. 79% of boluses were delivered per protocol in the 10 mL/kg arm and 55% in the 20 mL/kg arm. The volume of study bolus fluid after 4 hours was 44% lower in the 10 mL/kg group (mean 14.5 vs 27.5 mL/kg). The Paediatric Index of Mortality-2 score was 2.1 (IQR 1.6–2.7) in the 10 mL/kg group and 2.0 (IQR 1.6–2.5) in the 20 mL/kg group. There were no deaths. Length of hospital stay, paediatric intensive care unit (PICU) admissions and PICU-free days at 30 days did not differ significantly between the groups. In the perspectives study, the trial was generally supported, although some problems with protocol adherence were described.ConclusionsParticipants were not as unwell as expected. A larger trial is not feasible in its current design in the UK.Trial registration numberISRCTN15244462.

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“…Despite important reductions in the number of cases as a result of vaccination programs, Neisseria meningitidis (meningococcal) disease is still a major cause of invasive bacterial infections globally. 1,2 Complex interplays among host, pathogen, and environment determine the severity of disease. [3][4][5][6] The severity of infection ranges from harmless nasopharyngeal colonization to bacteremia, meningitis, sepsis, and lethal disease.…”

Section: Introductionmentioning

confidence: 99%

The Inflammatory and Hemostatic Response in Sepsis and Meningococcemia

Boeddha

Bycroft

Nadel

et al. 2020

Critical Care Clinics

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Complex interplays among host, pathogen, and environment determine the severity of infection ranging from harmless nasopharyngeal colonization to bacteremia, meningitis, sepsis, and lethal disease. The inflammatory response includes proinflammatory and anti-inflammatory responses in innate and adaptive immunity. The net proinflammatory state causes endothelial dysfunction and activation of the hemostatic response. Within the wide range of illness severity, deposition of fibrin throughout the microcirculation could result in multiple organ dysfunction, skin grafts/amputation, and death. Meningococci hold unique properties to promote adhesion, colonization, and invasion into the bloodstream.

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Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Abstract: European Union's Seventh Framework programme.

Cited by 65 publications

References 29 publications

Translating Sepsis-3 Criteria in Children: Prognostic Accuracy of Age-Adjusted Quick SOFA Score in Children Visiting the Emergency Department With Suspected Bacterial Infection

Translating Sepsis-3 Criteria in Children: Prognostic Accuracy of Age-Adjusted Quick SOFA Score in Children Visiting the Emergency Department With Suspected Bacterial Infection

Restricted fluid bolus volume in early septic shock: results of the Fluids in Shock pilot trial

The Inflammatory and Hemostatic Response in Sepsis and Meningococcemia

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