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Epidemiology of Sepsis & Inflammation

This group combines expertise on infections and inflammation in critically ill patients with a strong focus on epidemiological and methodological aspects of clinical research. Advanced statistics are used to study risk factors and mortality related to (nosocomial) infections as well as complications of sepsis. Novel molecular markers are used together with state-of-the-art epidemiological approaches to distinguish true infection from sterile inflammation, allowing for faster and more accurate diagnosis of infection as well as improved prognostication of critically ill patients in the ICU and/or patients in a postoperative setting. This group has expertise in innovative clinical trials in sepsis and inflammation.

Research interests/topics uitklapper, klik om te openen

We aim to improve early diagnosis and risk stratification of nosocomial infections occurring in critically ill and/or postoperative patients by using advanced mathematical modeling and novel biomarkers. Furthermore, we aim to advance the personalized management of sepsis and inflammation by studying novel treatments using adaptive platform trial design and a Bayesian statistical framework. Specific focus areas include:

  • Diagnostic uncertainty and early detection of sepsis
  • Attributable morbidity and mortality of (nosocomial) infections
  • Decision support for diagnosis and treatment of sepsis
  • New treatments for community-acquired pneumonia
  • Personalized medicine approaches

Keywords: Sepsis, inflammation, epidemiology, intensive care, critically ill patients, infection, biorepository, MARS, PLUTO, REMAP-CAP

About the group leader(s)

Prof. Olaf Cremer MD, PhD

Olaf Cremer (1971) was trained as an anesthesiologist, intensivist and clinical epidemiologist. He has worked as a consultant in the department of intensive care medicine of the UMC Utrecht since 2007. Since 2010 he has been studying the clinical epidemiology of infections in the ICU and/or the postoperative setting. He is one of the PI's of the MARS consortium, a multicenter collaboration aimed at developing new molecular technologies for early diagnosis and risk stratification of sepsis. More recently he initiated the PLUTO project, a longitudinal biorepository of patients undergoing elective surgery at UMC Utrecht.

Dr. Lennie Derde

Dr. Lennie Derde MD, PhD

Lennie Derde (1976) was trained as an internist, infectious diseases specialist and clinical epidemiologist before becoming an intensivist. She has worked as a consultant in the department of intensive care medicine of the UMC Utrecht since 2013. She has been involved in clinical trials in the field of infectious diseases, focusing on critically ill patients, since 2006. She is the European PI and the international trial steering committee chair of REMAP-CAP, a global adaptive platform trial aimed at finding the best treatment for community acquired pneumonia, including COVID-19.

Group members

Prof. dr. Marc Bonten
Dr. Maarten van Smeeden

Senior group members

Dr. Helen Leavis
Dr. Lisette Vernooij

PhD candidates

Meri Varkila, MSc
Nikki de Mul, MSc
Emma Rademaker, MSc
Diede Verlaan, MSc
Jelle Haitsma Mulier, MSc
Lara Pladet, MSc
Katja Scheffer, MSc
Brittney van der Woude, MSc

Key publications uitklapper, klik om te openen

Klein Klouwenberg PMC, van Mourik MSM, Ong DSY, Horn J, Schultz MJ, Cremer OL, Bonten MJM, MARS Consortium
Electronic implementation of a novel surveillance paradigm for ventilator-associated events. Feasibility and validation.
American Journal of Respiratory and Critical Care Medicine

van Vught LA, Klein Klouwenberg PMC, Spitoni C, Scicluna, BP, Wiewel MA, Horn J, Schultz MJ, Nürnberg P, Bonten MJM, Cremer OL, van der Poll T, for the MARS Consortium
Incidence, Risk Factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit After Admission for Sepsis
JAMA 2016; 315:1469-79

Koster-Brouwer ME, Verboom DM, Scicluna BP, van de Groep K, Frencken J, Janssen D, Schuurman R, Schultz MJ, van der Poll T, Bonten MJM, Cremer OL, on behalf of the MARS Consortium
Validation of a Novel Molecular Host Response Assay to Diagnose Infection in Hospitalized Patients Admitted to the ICU With Acute Respiratory Failure
Critical Care Medicine: March 2018;46(3):368-374

REMAP-CAP Investigators.
Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.
JAMA 2020; 324:1317–1329

REMAP-CAP Investigators.
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.
N Engl J Med 2021; 384:1491-1502

Achievements uitklapper, klik om te openen

Funding & Grants

2009 - Center for Translational Molecular Medicine (CTMM) - € 989.000
Molecular Diagnosis and Risk Stratification of Sepsis (MARS) Consortium

2014 - EU 7th Framework Programme (FP7-HEALTH-2013-INNOVATION-1) - € 4.9 mln.
The Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) (#602525)

2020 - Horizon 2020 (emergency CoV call) - € 14.8 mln.
Rapid European COVID-19 Emergency research Response (RECoVER) (#101003589)

2020 - ZonMw COVID-19 programma - € 596.000.
ANAkinra voor de behandeling van CORonavirus infectious disease 2019 op de Intensive Care (ANACOR-IC) (#10150062010003) 

2020 - Fonds Stichting Gezondheidszorg Spaarnestad (Zilveren Kruis) - € 253.000

Awards/Achievements/Prizes

2019 EPIMED solutions ESICM award for Olaf Cremer
Dr. Olaf Cremer received the 2019 EPIMED Solutions Award (€ 15.000) for quality improvement and patient safety for the project “Development of a dynamic prediction algorithm for early detection of ICU-Acquired Infections”.

Alumni / PhD theses uitklapper, klik om te openen

Novel Approaches for Diagnosing Sepsis in the Critically Ill
Diana M. Verboom
2020
Diana Verboom (1988, Putten) received her PhD on September 10, 2020 at Utrecht University. Supervisor was prof. dr. Marc Bonten (Julius Center for Health Sciences & Primary Care, UMC Utrecht) and co-supervisor was dr. Olaf Cremer (Intensive Care Department, UMC Utrecht).

Societal impact of sepsis and inflammation in the ICU and beyond
Marlies E. Koster-Brouwer
2019
Marlies Koster Brouwer (1989, Urk) received her PhD on October 22, 2019 at Utrecht University.  Supervisor was prof. dr. Marc Bonten (Julius Center for Health Sciences & Primary Care, UMC Utrecht) and co-supervisor was dr. Olaf Cremer (Intensive Care Department, UMC Utrecht).

Sepsis in the ICU: improving pathogen detection and understanding of infectious complications
Kirsten van de Groep
2019
Kirsten van der Groep (1988, Putten) received her PhD on October 22, 2019 at Utrecht University. Supervisor was prof. dr. Marc Bonten (Julius Center for Health Sciences & Primary Care, UMC Utrecht) and co-supervisor was dr. Olaf Cremer (Intensive Care Department, UMC Utrecht).

Studying the etiology of complications in sepsis
Jos F. Frencken
2018
Jos Frencken received his PhD on January 11, 2018 at Utrecht University.  Supervisor was prof. dr. Marc Bonten (Julius Center for Health Sciences & Primary Care, UMC Utrecht) and co-supervisor was dr. Olaf Cremer (Intensive Care Department, UMC Utrecht).

Opportunistic pathogens in the intensive care unit
David S.Y. Ong
2015
David Ong (1984, 's Gravenhage) received his PhD on December 8, 2015 at Utrecht University.  Supervisor was prof. dr. Marc Bonten (Julius Center for Health Sciences & Primary Care, UMC Utrecht) and co-supervisor was dr. Olaf Cremer (Intensive Care Department, UMC Utrecht).

Sepsis in intensive care patients: challenges in diagnosis and prognostication
Peter M.C. Klein Klouwenberg
2015
Peter Klein Kouwenberg (1976, Bergeijk) received his PhD on January 23, 2015 at Utrecht University. Supervisor was prof. dr. Marc Bonten (Julius Center for Health Sciences & Primary Care, UMC Utrecht) and co-supervisor was dr. Olaf Cremer (Intensive Care Department, UMC Utrecht).

Collaborations uitklapper, klik om te openen

Molecular Diagnosis and Risk Stratification of Sepsis (MARS) consortium, a collaboration with the Amsterdam UMC https://sepsisamsterdam.nl/

REMAP-CAP study group, part of the European Clinical Research Alliance on Infectious Diseases (ECRAID) initiative – Learn more

Perioperative longitudinal study of complications and long-term outcomes (PLUTO) study group, a collaboration between anesthesia and surgery departments in the UMC Utrecht  

Anesthesia Geriatric Evaluation (AGE) study group, a collaboration with St. Antonius Hospital Nieuwegein

Biomolecular Mass Spectrometry and Proteomics in Sepsis study group, a collaboration with Hecklab Utrecht

In the media uitklapper, klik om te openen

April 25, 2021 - VPRO Argos Medialogica - Lennie Derde
Analyse van REMAP-CAP laat zien dat hydroxychloroquine niet effectief is bij patienten met COVID-19 de IC

January 22, 2021 - www.nos.nl - Lennie Derde
REMAP-CAP laat zien dat hoge dosis bloedverdunners effectief is bij COVID-19 patienten die niet de IC liggen

November 19, 2020 - www.nos.nl - Lennie Derde
REMAP-CAP laat zien dat IL6-remmer tocilizumab is effectief is bij ernstig zieke patienten met COVID-19 op de IC

Contact information uitklapper, klik om te openen

Contact information regarding internships at this research group: research9@umcutrecht.nl

Prof. dr. Olaf Cremer

O.L.Cremer@umcutrecht.nl

+31 88-7561128

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