The early identification of disease progression in patients with suspected infection presenting to the emergency department: A multi-centre derivation and validation study

Research output: Contribution to journalArticle


Background: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. Methods: An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. Results: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0-207.6], 23.4 [11.1-49.3] and 32.6 [9.4-113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. Conclusions: In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.


  • Kordo Saeed
  • Darius Cameron Wilson
  • Frank Bloos
  • Philipp Schuetz
  • Yuri Van Der Does
  • Pierre Hausfater
  • Jacopo M. Legramante
  • Yann Erick Claessens
  • Deveendra Amin
  • Graham White
  • Beat Mueller
  • Maarten Limper
  • Carlota Clemente Callejo
  • Antonella Brandi
  • Marc Alexis MacChi
  • Nicholas Cortes
  • Alexander Kutz
  • Peter Patka
  • María Cecilia Yañez
  • Sergio Bernardini
  • Nathalie Beau
  • Matthew Dryden
  • Eric C.M. Van Gorp
  • Marilena Minieri
  • Louisa Chan
  • Pleunie P.M. Rood
  • Juan Gonzalez Del Castillo
External organisations
  • University of Southampton
  • Universitätsklinikum Jena
  • University of Basel
  • Erasmus University Medical Center
  • Skåne University Hospital
  • Tor Vergata University Hospital
  • University of Rome Tor Vergata
  • Monaco Princess Grace Hospital
  • Morton Plant Hospital
  • University Medical Center Utrecht
  • Hospital Clinico San Carlos de Madrid
  • St Bernard's Hospital
  • Brahms GmbH
  • Kantonsspital Aarau
  • Pitié-Salpêtrière University Hospital
  • North Hampshire Hospital
  • Utrecht University
  • Rare and imported pathogens laboratory (RIPL)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Anesthesiology and Intensive Care


  • Disease progression, Emergency department, MR-proADM, qSOFA, Sepsis, SOFA
Original languageEnglish
Article number40
JournalCritical Care
Issue number1
Publication statusPublished - 2019 Feb 8
Publication categoryResearch