Journal of Clinical Microbiology, 52(5), 1 May 2014, pp 1741-44, doi: 10.1128/JCM.03614-13
Intensive Care Medicine, 40(4), 1 April 2014, pp 564–571, doi: 10.1007/s00134-014-3225-8
Expert Opinion on Therapeutic Targets, 18(8), 1 August 2014, pp 851-61, doi: 10.1517/14728222.2014.925881

Project Documentation


Launch of R-GNOSIS, a European research project determining the efficacy and effectiveness of cutting-edge interventions to combat hospital infections and the spread of Multi-Drug resistant Gram-negative Bacteria (MDR-GNB)

The European community and health care settings are facing a dramatic increase in infections caused by MDR-GNB, with few effective therapeutic options remaining in the armamentarium of clinicians. There are no truly new antimicrobial agents against MDR-GNB expected on the market in the short or medium term. Even if new agents were to come to market, on their own, they could not solve the resistance problem. Effective measures to contain resistance and limit the spread of MDR-GNB are therefore urgently needed to protect the health and well-being of the people in Europe and world-wide. We are confronted with a formidable enemy, equipped with sophisticated molecular methods to express and exchange resistance genes, capable of colonizing multiple reservoirs, and harbouring a bewildering array of virulence factors to infect any suitable host, both the hospitalised frail and healthy people living in the community.

The R-GNOSIS programme

The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) project combines five international clinical intervention studies, all supported by highly innovative microbiology and mathematical modelling, to determine - in the most relevant patient populations - the efficacy and effectiveness of cutting-edge interventions to reduce acquisition, carriage, infection and spread of Multi-Drug Resistant Gram-negative Bacteria (MDR-GNB).
All clinical studies will progress science beyond the state-of-the-art in generating new and translational clinically relevant knowledge, through hypothesis-driven studies with a focus on patient-centred outcomes that matter to the people of Europe and beyond.
The studies and analyses proposed in R-GNOSIS will generate a step-change in identifying evidence-based preventive measures and clinical guidance for primary care and hospital-based physicians, as well as health-care authorities, to combat the spread and impact of the unprecedented rise of infections caused by MDR-GNB in Europe.

The proposed research program involves patients and clinicians, microbiologists and epidemiologists, infectious disease specialists, caregivers in inpatient care and mathematical modellers. The R-GNOSIS consortium is made of 20 partners from 9 countries which include Belgium, Denmark, France, Germany, Israel, Netherlands, Spain, Switzerland and United Kingdom.

The ambitions of R-GNOSIS

The European Centre for Disease Prevention and Control and the European Medicines Agency estimated that 193,300 patients were infected with MDR-GNB in 2007, and that these infections caused 18,200 excess deaths and 1,375,000 additional hospital days in EU Member States, Iceland and Norway. Moreover, the rate of infections caused by MDR-GNB is still increasing. Today, ‘more of the same’ research is therefore no longer an option. An “out-of-the-box” conceptual step-change is necessary. Evidence base needs to be optimised for “well known but inadequately researched” infection prevention strategies through innovative and state-of-the-art study designs. Counterintuitive and highly innovative, solutions need to be identified and rigorously evaluated.
The R-GNOSIS programme will concentrate on

  • the reduction of the prescription of antibiotics by family practitioners;
  • preventive administration of antibiotics to IC patients;
  • the usefulness of isolating patients who are carriers of ESBL bacteria and
  • the prevention of infections following abdominal operations.

R-GNOSIS will perform five pivotal international clinical intervention studies, each yielding a clear-cut solution, readily implementable in clinical practice, if proven effective. R-GNOSIS proposes innovative technology and a beyond state-of-the-art hypothesis-driven clinical approach.
Furthermore, R-GNOSIS will apply a ‘bedside-to-bench’ translational approach to study the impact of antibiotics and gut decolonization on MDR-GNB pathogens and commensals in the community or hospital utilizing state-of-the-art microbiological tools. Results from the diagnostic interventions planned here will revolutionize current screening practices for MDR-GNBs in hospitals and introduce the use of point-of-care testing in primary care.
Finally, R-GNOSIS will facilitate ground-breaking modelling studies, in which nosocomial transmission capacities for different species of MDR-GNB during different interventions will be quantified. Within-host models of bacterial dynamics and gene transfer (based on in vivo and in vitro experiments) will be combined with between-host models, both for hospitals and the community. These integrated models will be used to provide projections of long-term impacts of interventions.

For more information:

R-GNOSIS website:

Contact details:

Scientific and Research Project Coordinator:
Prof Marc J.M. Bonten
University Medical Center Utrecht
Heidelberglaan 100
3584 CX Utrecht
The Netherlands
Phone: +31 88 7557394

R-GNOSIS Project Office:
Andrea Kuperberg
58A, rue du Dessous des Berges
F-75013 Paris
Phone: +33 1 53945484