The aim of ARTE is to deliver effective antimicrobial therapy by providing a bench-to-bedside platform for state-of-the-art research, education and training in antimicrobial resistance and therapeutics. This aim is driven by the current problems faced by society and individual patients with respect to the growing threat of global antibiotic resistance.
Research Activities
The primary aim of research of ARTE is to provide a platform for research in antimicrobial resistance and therapeutics in all its aspects from bench to bedside and back. ARTE is therefore by definition multidimensional and multidisciplinary:
Clinical – Advice to clinicians via dedicated Antibiotic-teams (‘A-teams’); development of software to increase the quality of care and provide clinical decision; optimization of antimicrobial treatments and improvement of infectious disease diagnoses.
Epidemiological – Mapping the carriage of antibiotic resistance genes; identifying risk factors for the acquisition, carriage and spread/transfer of these resistance genes - all supported by various molecular identification and typing techniques.
Fundamental – Studying antibiotic resistance mechanisms, the development of new antibiotics and novel treatment strategies; studies into microbial virulence and microbe/host interactions.
Translational – Development of clinical implementation strategies including pharmacokinetic/-pharmacodynamic antibiotic studies using novel in vitro, in vivo and patient-simulating model systems; development and validation of new rapid/point-of-care (POCT) diagnostic devices/techniques.
Funding continues to be obtained from a wide range of funding bodies, including: Industrial (e.g. MSD); European (e.g. H2020); National (e.g. N.W.O., ZonMW); Local (e.g. Erasmus Foundation) and Non-Governmental organisations. A few examples include: Diagnostics and Surveillance of Antimicrobial Resistance (178k €, Dr. Severin); Targeting Mycobacterium tuberculosis (493k €, Dr. de Steenwinkel); Optimising Hand Hygiene in Hospitals (198k €,Prof. Vos); Development of Tailored Antimicrobial Treatment Regimens and Novel Host- Pathogen InsightsFor Respiratory Tract Infections And Sepsis (1,412k €, Dr. Hays); Demonstration of intelligent decision support for pandemic crisis prediction and management within and across European borders (161k €, Dr. Louwen).
Collaborations
ARTE performs research together with local, national and international partners and is an active member of the Netherlands Centre of OneHealth. ARTE participates in, and continues to initiate, international research collaborations (e.g. PreDiCT-TB, DIAGORAS, NACTAR, MACOTRA, SAPMAN, FLEMING-Indonesia, FLEMING-Vietnam, GNA NOW, Nest-NET). Its principal investigators have been coordinators or partners in several large European funded projects (e.g. AIDA, CO-ACTION, STAMINA, GNA NOW, InSPECtion, NABARSI, TAILORED-Treatment, COMBACTE, EU-PEARL).
Contributions
ARTE is involved in education at all levels at the Erasmus MC and its partners. For Bachelor programmes, ARTE is involved in the BSc Medicine (main theme Infection & Immunity) and the Medical Delta BSc Clinical Technology (theme Microbial Diagnostics and Techniques). For Master programmes , ARTE participates in the MSc Infection & Immunity (as part of the Postgraduate School Molecular Medicine). Many PhD students within the different research areas of ARTE are also involved in receiving ARTE-specific education.
Further, education is not limited to the Erasmus MC per se, as national high level courses are organized to increase awareness of antibiotic resistance and the various therapeutic options available. Members of ARTE also have a long tradition of promoting internationalisation by organizing and participating in courses at the European level. For example, ARTE currently provides more than 50 ‘minor’ study opportunities all over the world, with a strong focus on developing countries. In particular, there are strong ties with several Indonesian Universities, including student exchanges. Examples of the results of such collaborations include two joint educational Fleming projects (one with Indonesian partners and another one with Vietnamese partners). Finally, the education and training of medical microbiology specialists together with infectious disease specialists, (in the same department) is unique within the Netherlands.
Care Activities
ARTE has the objective of providing improved care for the following patient populations: intensive care patients; patients where research is closely associated with patient care; multi-specialism care patients; patients presenting with rare diagnoses; patients who are referred to Erasmus MC by medical specialists and patients younger than 50 years of age presenting with 3 or more diseases.
According to VBHC criteria, quality improvement generated health outcomes are powerful drivers of cost containment and value improvement. In this respect, ARTE helps promote the following quality improvements: early detection, correct diagnosis, correct treatment to the correct patient; and treatment earlier in the causal chain of disease. Further, our emphasis on preventing the inappropriate use of antibiotics and reducing the appearance of antibiotic resistance fits well with the statements that 'Better health is the goal, not more treatment' and 'Better health is inherently less expensive than poor health'.
ARTE currently researches into the current and future threats of antibiotic-resistant pathogens, rapid and Point-of-Care diagnostics, as well as the development of new antibiotics and treatments. Further, advice is provided by our Antimicrobial Stewardship Teams. The Unit Diagnostics Medical Microbiology obtained ISO accreditation in 2013 as a first in The Netherlands and this was later followed by the Unit Research and Diagnostics.
Societal Relevance to Research, Education and Patient Care
In the influential O'Neill report from the UK government (2016), antimicrobial resistance was recognized as the most important threat to human medicine with an impact in all areas of patient care, including in veterinary medicine and related fields. Erasmus MC has recognized the importance of this global phenomenon by active participation in the Netherlands Centre of One Health (NCOH). ARTE plays an important role in the NCOH, including participation in the BRICK project (Dr. Willem van Wamel) and project RvB-NCOH (Dr. Jaap van Hellemond).
Members of ARTE are active in the European arena and have several leading positions in national and international committees. At a national level, members of ARTE are strongly represented in ‘SWAB’, the Dutch Society for the prudent use of Antibiotics, as well as the AMR working group. The guidelines formulated by SWAB are leading in generating antimicrobial therapy protocols in the Netherlands and the continual development of SWAB-ID (a web based formularium used by more than half of the hospitals in The Netherlands) was developed with its roots at the EMC.
ARTE staff members continue to contribute to information campaigns aimed at societal target groups. A few examples are: 1) multiple interviews for Dutch television and newspapers (e.g. Dr. Severin (Algemeen Dagblad) and Dr. Louwen (Bionieuws); 2) the MAIL-project of the IP&AMR Care Network Southwest Netherlands (IP&ABR Zorgnetwerk Zuidwest-Nederland) aimed to improve communication on the topic of antimicrobial resistance from healthcare institutions to patients (supervised by Dr. Severin). The output of the project is a set of communication materials that was made publicly available in 2020 at https://www.abrzorgnetwerkzwn.nl/mail/.
Viability of Research, Education and Patient Care
ARTE aims to increase the viability of international antimicrobial resistance research, education and patient care. Members of ACE work together with colleagues in many different disciplines, with a good mix between younger and more experienced scientists, participating in many different international, European and JPI-AMR projects.
ARTE has shown the potential for attracting new people at all levels including students, research scientists, molecular/medical biologists and medical doctors. ARTE provides opportunities for international PhD students (including from Indonesia, Australia, Spain etc.) as well as Post-doctoral and senior scientists (including from Greece, Italy etc.). Finally, international networking is key to the success of ARTE with PhD students being encouraged to follow international courses and gain experience abroad during their training.
Key and relevant publications of the last five years
- C-Reactive Protein, Procalcitonin, and White Blood Count to Rule Out Neonatal Early-onset Sepsis Within 36 Hours: A Secondary Analysis of the Neonatal Procalcitonin Intervention Study. Stocker M, van Herk W, El Helou S, Dutta S, Schuerman FABA, van den Tooren-de Groot RK, Wieringa JW, Janota J, van der Meer-Kappelle LH, Moonen R, Sie SD, de Vries E, Donker AE, Zimmerman U, Schlapbach LJ, de Mol AC, Hoffman-Haringsma A, Roy M, Tomaske M, F Kornelisse R, van Gijsel J, Visser EG, Plötz FB, Heath P, Achten NB, Lehnick D, van Rossum AMC. Clin Infect Dis. 2020 Sep 3:ciaa876. doi: 10.1093/cid/ciaa876. Online ahead of print.
- 100% Single-Patient Rooms and Environmental Contamination With Highly Resistant Microorganisms: The MOVE Study. Van der Schoor, A., Voor in ‘t holt, A., Severin, J., Gommers, D., Bruno, M., Hendriks, J., & Vos, M. (2020). Infection Control & Hospital Epidemiology, 41(S1), S91-S92. doi:10.1017/ice.2020.588
- Mortality associated with carbapenem-susceptible and Verona Integron-encoded Metallo-β-lactamase-positive Pseudomonas aeruginosa bacteremia. Persoon, M.C., Voor in’t holt, A.F., Wielders, C.C.H., Diederik Gommers, Margreet C. Vos & Juliëtte A. Severin Antimicrob Resist Infect Control 9, 25 (2020). https://doi.org/10.1186/s13756-020-0682-4
- Isothermal microcalorimetry minimal inhibitory concentration testing in Extensively drug resistant Gram-negative bacilli: a multicentre study. C. Tellapragada, B. Hasan, A. Antonelli, A. Maruri, C. de Vogel, D. Gijón, M. Coppi, A. Verbon, W. van Wamel, G.M. Rossolini, R. Cantón, C.G. Giske, Clinical Microbiology and Infection, Volume 26, Issue 10, 2020, Pages 1413.e1-1413.e7, ISSN 1198-743X, https://doi.org/10.1016/j.cmi.2020.01.026.
- Superior Efficacy of a Bedaquiline, Delamanid, and Linezolid Combination Regimen in a Mouse Tuberculosis Model. Elise D Pieterman, Lina Keutzer, Aart van der Meijden, Sanne van den Berg, Han Wang, Matthew D Zimmerman, Ulrika S H Simonsson, Hannelore I Bax, Jurriaan E M de Steenwinkel, The Journal of Infectious Diseases, 2021;, jiab043, https://doi.org/10.1093/infdis/jiab043
- Guide-free Cas9 from pathogenic Campylobacter jejuni bacteria causes severe damage to DNA. Chinmoy Saha, Prarthana Mohanraju, Andrew Stubbs, Gaurav Dugar, Youri Hoogstrate, Gert-Jan Kremers, Wiggert A. van Cappellen, Deborah Horst-Kreft, Charlie Laffeber, Joyce H.G. Lebbink, Serena Bruens, Duncan Gaskin, Dior Beerens, Maarten Klunder, Rob Joosten, Jeroen A. A. Demmers, Dik van Gent, Johan W. Mouton, Peter J. van der Spek, John van der Oost, Peter van Baarlen and Rogier Louwen. Science Advances 2020: Vol. 6, no. 25, eaaz4849 DOI: 10.1126/sciadv.aaz4849
- Therapeutic Efficacy of Novel Antimicrobial Peptide AA139-Nanomedicines in a Multidrug Resistant Klebsiella pneumoniae Pneumonia-Septicemia Model in Rats. Hessel van der Weide, Unai Cossío, Raquel Gracia, Yvonne M. te Welscher, Marian T. ten Kate, Aart van der Meijden, Marco Marradi, Jeffrey A. S. Ritsema, Denise M. C. Vermeulen-de Jongh, Gert Storm, Wil H. F. Goessens, Iraida Loinaz, Cornelus F. van Nostrum, Jordi Llop, John P. Hays, Irma A. J. M. Bakker-Woudenberg Antimicrobial Agents and Chemotherapy Aug 2020, 64 (9) e00517-20; DOI:10.1128/AAC.00517-20
- New-Generation Antibiotics for Treatment of Gram -Positive Infections: A Review with Focus on Endocarditis and Osteomyelitis. Bloem A, Bax HI, Yusuf E, Verkaik NJ. J Clin Med. 2021 Apr 17;10(8):1743. doi: 10.3390/jcm10081743. PMID: 33920526; PMCID: PMC8074169.
- Neonatal Staphylococcus aureus acquisition at a tertiary intensive care unit. Bibi C.G.C. Slingerland, Nelianne J. Verkaik, Corné H.W. Klaassen, Willemien H.A. Zandijk, Irwin K.M. Reiss, Margreet C. Vos. American Journal of Infection Control, Volume 48, Issue 9, 2020, Pages 1023-1027, ISSN 0196-6553, https://doi.org/10.1016/j.ajic.2019.11.011. (https://www.sciencedirect.com/science/article/pii/S0196655319309770)
- Cefpirome treatment results in limited selection of stable derepressed Enterobacter cloacae mutants in the intestinal flora of rats treated for an experimental K. pneumoniae pulmonary infection. Vikas Gautam, Johan W. Mouton, M. Ten Kate, I. Bakker-Woudenberg, Nikolaos Strepis, Corné H. Klaassen and Wil Goessens. 2020. Microbial Drug Resistance 26(4):341-348.
PhD theses of the last five years
- Saharman, Y.R. (clinical microbiology) (2020, november 27). ICU-acquired Carbapenem-non-susceptible Bacilli in Indonesia Focus on: Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. EUR Prom./coprom.: Prof. Dr. H.A. Verbrugh, Dr.Phd J.A. Severin & A. Karuniawati. http://hdl.handle.net/1765/132401 (IR)
- Weide, H. van der (clinical microbiology) (2020, september 30). Development of novel nanomedicines based on antimicrobial peptides for the treatment of multidrug-resistant Gram-negative pneumonia. EUR Prom./coprom.: Prof. Dr. A. Verbon & Dr. J.P. Hays. http://hdl.handle.net/1765/130462 (IR)
- Yahiaoui, R.Y. (clinical microbiology) (2020, december 2). Streptococcus pneumoniae Carriage and Effect of Vaccination on Prevalence, Serotypes and Antibiotic Resistance. EUR Prom./coprom.: Prof. Dr. A. Verbon & E.E. Stobberingh. http://hdl.handle.net/1765/131086 (IR)
- Velde de F Dosing optimization of beta-lactam antibiotics using parametric and nonparametric population pharmacokinetic models Promotor: Prof. dr. J.W. Mouton, Prof. dr. A. Verbon, Prof. dr. T. van Gelder Co-promotoren: Dr. B.C.P. Koch, Dr. A.E. Muller PhD Thesis EUR Rotterdam; (T1), 14 oktober 2020
- Slingerland BCGC Golden Staph, colonization, carriage and transmission Promotor: Prof. dr. M.C. Vos Co-promotor: Dr. W.J.B. van Wamel PhD Thesis EUR Rotterdam; (T1), 11 november 2020