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
It is known that treating patients with antibiotics is associated with the emergence of resistance - and worse outcomes for patients. But how resistance emerges during infections remains poorly understood.
Now a study published in Nature Communications reports that rapid bacterial evolution interacts with host immunity to shape both the rise, and fall, of resistance during infection. ###This study was performed as part of the IMI COMBACTE-MAGNET project.
COMBACTE-MAGNET is working to find new approaches to combat antibiotic resistance. This new study highlights the need to understand better how our immune system works with antibiotics to suppress bacterial infections.
The research described in the article is part of the ASPIRE-ICU study, which stands for Advanced understanding of Staphylococcus aureus and Pseudomonas aeruginosa Infections in EuRopE – Intensive Care Units.
Find out more
- Read the article in full
Antimicrobial resistance (AMR) project COMBACTE-MAGNET has launched a new, freely accessible online tool that allows healthcare professionals and the public to assess the risk of international travellers acquiring (and spreading) antimicrobial-resistant bacteria.###
Travel plays a major role in the spread of AMR, and the new AMR Travel Tool will make it easier for healthcare professionals to evaluate patients’ travel history and associated AMR risk factors. The healthcare professional’s section of the website highlights differences in resistance levels between the travel destination and the host country, for example.
Meanwhile, travellers can enter their travel destination and receive general advice on infection control as well as pathogen-specific advice on the infection risks related to their destination (and tips on how to avoid them).
Find out more
- Visit the AMR Travel Tool
COMBACTE projects have launched a unique European platform that allows users to explore and visualise data on antibiotic resistant infections in humans and animals across Europe. The website, which is freely accessible, brings together epidemiology data from 32 European countries on the priority list of pathogens released by the World health Organization in 2017.### It also includes data on more recent outbreaks and emerging cases of resistance to newly-developed antibiotics. Data is displayed via colour-schemed maps that allow users to easily track things like the setting, resistance rates, sample sizes and data sources. If users register, they can also select and download data. In a statement, the project explains: ‘The goal is to give industry, policy makers, and public an easy tool to use in order to understand the trends and the epidemiology of antimicrobial resistant infections across Europe using a One Health approach. The platform provides an interactive space, which combines multiple sources and allows to overcome language barriers.’
Antibiotic resistance is a big global public health problem. Of particular concern are multidrug-resistant Gram-negative bacteria, which are among the leading causes of serious, debilitating and life threatening healthcare-associated infections. There is an urgent need for new therapies to treat or prevent infections caused by these bacteria in hospitalised patients. IMI’s COMBACTE-MAGNET project is developing new antibacterial treatments for vulnerable patients, especially the critically ill in intensive care units. ###It is doing this by promoting collaborations between scientific experts. ‘I think the creation of an effective public-private consortium like COMBACTE-MAGNET in itself is a major achievement,’ says project coordinator Hasan Jafri of MedImmune, the global biologics research and development arm of AstraZeneca. ‘The project brings together top researchers and clinicians from five pharmaceutical companies – AstraZeneca, AiCuris, GSK, Basilea Pharmaceutica, and Sanofi – and more than 30 leading academic medical centres from 10 European countries.’ To date, the COMBACTE-MAGNET consortium has established a Pan-European platform called EPI-Net to access epidemiological data; is publishing the first results from an epidemiology study; and is designing innovative clinical trials to advance development of novel molecules against multidrug-resistant Gram-negative bacteria.
- Read the entire story
The Antibacterial Resistance Leadership Group (ARLG) has become the first US consortium to take part in clinical studies run by IMI’s COMBACTE programme on antimicrobial resistance. In a statement, the project described the news as a ‘major milestone’ that ‘clearly demonstrates the benefits of public-private collaboration and international collaboration between COMBACTE and ARLG’. ###The ARLG is joining two studies on treatments design to prevent pneumonia in people in intensive care who require a ventilator to help them breathe. The SAATELLITE study focuses on pneumonia caused by Staphylococcus aureus, while EVADE focuses on infections caused by Pseudomonas aeruginosa. Currently, 15 US sites are slated to participate in the trials; the first, in Detroit, was activated in January. ‘It is becoming increasingly common for hospitalised patients—especially those with weakened immune systems—to develop severe, hard-to-treat bacterial infections,’ said Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID) which is supporting the ARLG’s participation in the studies. ‘These clinical trials […] are part of a global collaborative effort to explore innovative ways to mitigate the threat of antimicrobial resistance.’ Meanwhile COMBACTE-NET coordinator Hasan Jafri of MedImmune said: ‘We believe collaboration with world-renowned experts, such as those within COMBACTE and the ARLG, is one of the best models to advance development in this area, and bring novel and effective anti-infectives to patients.’
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.
Meet COMBACTE at ECCMID!
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.’
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.
ParticipantsShow participants on map
- Aicuris Anti-Infective Cures AG, Wuppertal, Germany
- Astrazeneca AB, Södertälje, Sweden
- Basilea Pharmaceutica International AG, Basel, Switzerland
- Glaxosmithkline Research And Development LTD., Brentford, Middlesex, United Kingdom
- Sanofi-Aventis Recherche & Developpement, Chilly Mazarin, France
Universities, research organisations, public bodies, non-profit groups
- Academisch Medisch Centrum Bij De Universiteit Van Amsterdam, Amsterdam, Netherlands
- Assistance Publique Hopitaux De Paris, Paris, France
- Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
- Centre hospitalier universitaire de Limoges, Limoges, France
- Clinique Universitaire Saint-Luc Asbl, Brussels, Belgium
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Barcelona, Spain
- Eberhard Karls Universitaet Tuebingen, Tuebingen, Germany
- Erasmus Universitair Medisch Centrum Rotterdam, Rotterdam, Netherlands
- Fondazione PENTA - for the treatment and care of children with HIV-ONLUS, Padova, Italy
- Inst Cardiometabolisme Nutrition Ican, Paris, France
- Institut Catala De La Salut, Barcelona, Spain
- Institut National De La Sante Et De La Recherche Medicale, Paris, France
- Medizinische Universitaet Wien, Vienna, Austria
- North Bristol National Health Service Trust, Bristol, United Kingdom
- Servicio Andaluz De Salud, Sevilla, Spain
- Stichting Radboud Universiteit, Nijmegen, Netherlands
- Tel Aviv University, Tel Aviv, Israel
- The University Of Liverpool, Liverpool, United Kingdom
- Universita Degli Studi Di Verona, Verona, Italy
- Universitaet Ulm, Ulm, Germany
- Universitaetsklinikum Freiburg, Freiburg, Germany
- Universitair Medisch Centrum Utrecht, Utrecht, Netherlands
- Universitat Zurich, Zürich, Switzerland
- Universite De Geneve, Genève 4, Switzerland
- Universiteit Antwerpen, Antwerp, Belgium
- University College London, London, United Kingdom
- University Of The West Of England, Bristol, Bristol, United Kingdom
- University of Oxford, Oxford, United Kingdom
Small and medium-sized enterprises (SMEs)
- TranScrip Partners LLP, Reading, United Kingdom
- Ursula Theuretzbacher, Vienna, Austria
- Hospital Clinico Y Provincial De Barcelona, Barcelona, Spain
- Universite Paris Cite, Paris, France
Non EFPIA companies
- European Forum For Good Clinical Practice, Brussels, Belgium
- Royal Liverpool And Broadgreen University Hospitals Nhs Trust, Liverpool, United Kingdom
- Servei De Salut De Les Illes Balears, Palma, Spain
- Servicio Madrileno De Salud, Madrid, Spain
|Name||IHI funding in €|
|Academisch Medisch Centrum Bij De Universiteit Van Amsterdam||618 750|
|Assistance Publique Hopitaux De Paris||180 858|
|Centre hospitalier universitaire de Limoges||25 596 174|
|Centre Hospitalier Universitaire Vaudois||157 800|
|Clinique Universitaire Saint-Luc Asbl||542 997|
|Consorci Institut D'Investigacions Biomediques August Pi I Sunyer||281 462|
|Eberhard Karls Universitaet Tuebingen||1 173 200|
|Erasmus Universitair Medisch Centrum Rotterdam||29 971|
|European Forum For Good Clinical Practice||120 000|
|Fondazione PENTA - for the treatment and care of children with HIV-ONLUS||418 665|
|Inst Cardiometabolisme Nutrition Ican||346 900|
|Institut Catala De La Salut||186 438|
|Institut National De La Sante Et De La Recherche Medicale||196 500|
|Medizinische Universitaet Wien||234 672|
|North Bristol National Health Service Trust||1 150 484|
|Royal Liverpool And Broadgreen University Hospitals Nhs Trust||3 820|
|Servei De Salut De Les Illes Balears||375 000|
|Servicio Andaluz De Salud||1 054 885|
|Servicio Madrileno De Salud||133 997|
|Stichting Radboud Universiteit||776 911|
|Tel Aviv University||71 994|
|The University Of Liverpool||166 886|
|TranScrip Partners LLP||8 522|
|Universita Degli Studi Di Verona||1 890 592|
|Universitaet Ulm||188 550|
|Universitaetsklinikum Freiburg||543 600|
|Universitair Medisch Centrum Utrecht||5 765 921|
|Universitat Zurich||148 050|
|Universite De Geneve||622 761|
|Universiteit Antwerpen||2 752 750|
|University College London||27 435|
|University of Oxford||195 000|
|University Of The West Of England, Bristol||343 466|
|Ursula Theuretzbacher||88 681|
|Name||Funding in €|
|Hospital Clinico Y Provincial De Barcelona||174 338|
|Universite Paris Cite||157 500|
|Total Cost||46 725 530|