Combatting bacterial resistance in Europe - molecules against Gram negative infections


Start Date
End Date
IMI1 - Call 11
Grant agreement number

IMI Funding
75 340 000
EFPIA in kind
91 662 413
930 294
Total Cost167 932 707


Antimicrobial resistance (AMR) is a major global public health threat and there is a rapid emergence and spread of multidrug resistant (MDR) bacterial infections. Patients in intensive care units (ICUs) are particularly vulnerable to infections, for example in their lungs and airways. Increasingly, these infections are resistant to a range of antibiotics, leaving doctors with few options to treat their patients. The COMBACTE-MAGNET project is evaluating a new approach to preventing and treating life-threatening infections caused by Gram-negative bacteria. It is also setting up a pan-European epidemiological network called ‘EPI-Net’ that will help to optimise the surveillance of antibiotic resistance and healthcare associated infections in Europe.

Antimicrobial resistance (AMR) represents a serious and growing threat to human and animal health worldwide. In the EU alone, AMR is responsible for some 25 000 deaths every year, and the annual treatment and social costs have been estimated at €1.5 billion. Meanwhile, new forms of resistance continue to arise and spread, leaving clinicians with few weapons to bring infections under control. Yet despite the recognised need for new antibiotics, the reality is that only two new classes of antibiotics have been brought to the market in the last three decades.

Critically-ill patients in hospital intensive care units (ICUs) are particularly prone to infections of the lungs and airways, urinary tract, and intra-abdominal area. Very often, these infections are caused by so-called ‘Gram-negative’ bacteria, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. These bacteria are increasingly proving resistant to antibiotics, meaning there is an urgent need for new treatment options. However, the antibiotic development pipeline is running dry.

COMBACTE-MAGNET – focus on intensive care patients

The COMBACTE-MAGNET project takes a new approach to preventing P. aeruginosa infections, especially pulmonary infections in ICU patients, and treating patients with life-threatening infections caused by MDR Gram-negative bacteria, including P. aeruginosa.

The project will link up with and add to the pan-European clinical and laboratory networks (CLIN-Net and LAB-Net) set up by COMBACTE, one of the first projects in IMI’s antimicrobial resistance programme New Drugs for Bad Bugs (ND4BB). COMBACTE-MAGNET will also oversee the creation of a new network called EPI-Net, which will map and connect existing surveillance systems in Europe to optimise efforts to monitor the spread of antibiotic resistance and healthcare-associated infections. EPI-Net will draw on the expertise of a range of stakeholders to develop harmonised measures for the surveillance of healthcare associated infections in Europe.

Hope for new antibacterials

Two novel compounds will be developed through clinical trials carried out in COMBACTE-MAGNET.

The first, MEDI3902 (developed by MedImmune, AstraZeneca), is a promising new anti-bacterial monoclonal antibody for the treatment of P. aeruginosa infections, especially pulmonary infections, in ICU patients. The project team will carry out Phase 2 and 3 trials in adult ICU patients; these trials, involving larger numbers of patients are designed to gather information on the safety and efficacy of the medicine. The project will also carry out a Phase 1 study of MEDI3902 in children; this study, involving only a small number of children, focuses primarily on safety and understanding how the drug is processed by the body in children.

The second drug, AIC499 (developed by AiCuris), a new beta-lactam antibiotic has shown to be effective against a broad range of MDR Gram-negative bacteria. COMBACTE-MAGNET will carry out Phase 1 and Phase 2 trials to assess its safety and efficacy of AIC499. If the trial results are positive, AIC499 could prove useful in the treatment of patients with life-threatening infections.

The clinical studies of MEDI3902 and AIC499 will be supported by additional research that will shed new light on the consequences of P. aeruginosa infections. They will also study factors that influence how different patients respond to infection.

An urgent need

Patients in intensive care are already seriously ill, and infection with a multi-drug resistant bug can prove fatal. COMBACTE-MAGNET brings together leading researchers from academia and industry, and has strong ties with the other projects in IMI’s ND4BB programme as well as other relevant networks. As such it is well placed to advance the development of new, life-saving treatment options for this vulnerable group of patients.

Achievements & News

COMBACTE-MAGNET launches clinical study of promising antibiotic
January 2017

Scientists from IMI’s antimicrobial resistance project COMBACTE-MAGNET have launched a clinical study of a promising antibiotic called AIC499. Developed by German company AiCuris, the drug appears to be effective against a range of multi-drug resistant bacteria in complicated urinary tract infections and intra-abdominal infections.### A phase I trial to evaluate the safety of AIC499 in healthy volunteers is now underway at the Medical University of Vienna in Austria. AIC499 is designed to tackle so-called Gram-negative bacteria, which are surrounded by a tough cell wall that forms a solid defence against many antibiotics. ‘Gram-negative pathogens are considered to be amongst the most serious threats to public health and a major unmet medical need,’ said AiCuris CEO Holger Zimmermann. ‘We are convinced that, with its unique profile and extensive coverage, AIC499 has the potential to become a highly effective antibiotic for patients with severe infections including those caused by multi-resistant pathogens.’ The first results from this Phase I study should be available in mid-2017.

IMI’s COMBACTE family of antimicrobial resistance projects will have a stand at the exhibition of the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Vienna, Austria on 22-25 April. ###The project team will be at booth 29 at the exhibition. Partners in the COMBACTE-MAGNET project will also present results from their RESCUING study at the conference. RESCUING gathered observational data on the treatment of some 1 000 patients with complicated urinary tract infections in 8 countries where the prevalence of multidrug-resistant Gram-negative bacteria is seen to be high. That includes Bulgaria, Greece, Hungary, Israel, Italy, Romania, Turkey and Spain. In a blog post on the COMBACTE website, COMBACTE-NET’s Bruno François explains why COMBACTE is going to ECCMID: ‘Since ECCMID is one of the biggest, most important microbiology and infectious diseases congresses, I would say it is really ‘the place to be’ for our project. Without a doubt it also creates more visibility. Next to that, the event itself fits with the purpose of COMBACTE.’
(March 2017)

COMBACTE-MAGNET project gets underway
The COMBACTE-MAGNET project has got underway with the goal of contributing to efforts to tackle certain types of drug-resistant infections. Specifically, the 7 year, €167 million project will investigate a new approach to preventing respiratory infections in patients in intensive care units and new treatment options for patients with life-threatening infections caused by multi-drug resistant bacteria. ###The project will also trial two new medicines: MedImmune’s MED3902 and AiCuris’s AIC499. More broadly, the project will build on the clinical trial and laboratory networks established by COMBACTE and set up a new network called EPI-Net. EPI-Net will map and draw on existing surveillance systems in Europe to optimally describe the epidemiology of antibiotic resistance and healthcare associated infections.
(February 2015)

Participants Show participants on map

EFPIA companies
  • AiCuris Anti-infective Cures GmbH, Wuppertal, Germany
  • AstraZeneca AB, Södertälje, Sweden
  • Basilea Pharmaceutica International AG, Basel, Switzerland
  • Glaxosmithkline Research And Development LTD, Brentford, Middlesex, United Kingdom
  • Sanofi-Aventis Research and Development, Chilly Mazarin, France
Universities, research organisations, public bodies, non-profit groups
  • Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam, Netherlands
  • Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
  • Centre Hospitalier Universitaire de LIMOGES, Limoges, France
  • Cliniques Universitaires Saint Luc, Brussels, Belgium
  • Consorci Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
  • Eberhard Karls Universitaet Tuebingen, Tuebingen, Germany
  • Erasmus Universitair Medisch Centrum Rotterdam, Rotterdam, Netherlands
  • European Forum for Good Clinical Practice, Brussels, Belgium
  • Fondazione PENTA - for the treatment and care of children with HIV-ONLUS, Padova, Italy
  • Hospital Universitario Son Espases, Palma, Spain
  • Hôpital de la Salpêtrière, Paris , France
  • Institut Català De La Salut, Barcelona, Spain
  • Institut National De La Sante Et De La Recherche Medicale, Paris, France
  • Institute of Cardiometabolism And Nutrition, Paris, France
  • Medizinische Universitaet Wien, Vienna, Austria
  • North Bristol National Health Service Trust, Bristol, United Kingdom
  • Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom
  • Servicio Andaluz de Salud, Sevilla, Spain
  • Servicio Madrileno De Salud-Fibhug, Madrid, Spain
  • Stichting Katholieke Universiteit / Radboud university medical center, Nijmegen, Netherlands
  • Tel Aviv University, Tel Aviv, Israel
  • Universitaet Ulm, Ulm, Germany
  • Universitaet Zuerich, Zürich, Switzerland
  • Universitaetsklinikum Freiburg, Freiburg, Germany
  • Universitair Medisch Centrum Utrecht , Utrecht, Netherlands
  • Universiteit Antwerpen, Antwerp, Belgium
  • University College London, London, United Kingdom
  • University of Liverpool, Liverpool, United Kingdom
  • University of Oxford, Oxford, United Kingdom
  • University of the West of England, Bristol, United Kingdom
  • Université de Genève, Genève 4, Switzerland
Small and medium-sized enterprises (SMEs)
  • TranScrip Partners LLP, Reading, United Kingdom
  • Ursula Theuretzbacher, Vienna, Austria
Third parties
  • Université Paris Diderot-Paris 7, Paris, France


Project coordinator
Hasan Jafri
AstraZeneca AB
Managing entity
Marc J.M. Bonten
University Medical Center Utrecht