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.
In many cases, where infections are already resistant to many antibiotics, the treatment of last resort is a class of antibiotics called carbapanems. Unfortunately, recent years have seen a rise in cases of infections caused by bacteria known as carbapanem-resistant enterobacteriaceae (CRE) that, as their name suggests, are resistant to carbapanems. CRE infections are most common in healthcare settings. They are extremely hard to treat (very often the only treatment options are combinations of old, toxic antibiotics) and can be fatal.
According to the European Centre for Disease Prevention and Control (ECDC), cases of CRE infections have been reported in most European countries and rates of CRE infections are on the rise.
Focus on the toughest resistant infections
CRE infections form the focus of the COMBACTE-CARE project. Simply detecting CRE infections is challenging, as CRE bacteria are extremely diverse. With this in mind, one challenge for the COMBACTE-CARE team will contribute to both the rapid detection and characterisation of CRE infections. They will also work to deliver new knowledge on biological markers that predict which patients with the most serious healthcare-associated infections are at risk of poor outcomes.
More broadly, the project will analyse clinical and microbiological data to make recommendations for the development of novel antibiotics to treat resistant infections. They will also carry out research on the clinical management and outcomes of hospitalised patients (including newborn babies, children, and adults) with serious infections to identify the best available treatments.
COMBACTE-CARE forms part of IMI’s wider New Drugs for Bad Bugs (ND4BB) programme, and will work closely with and build on the pan-European clinical and laboratory networks (CLIN-Net and LAB-Net) set up by the COMBACTE project. COMBACTE-CARE will focus specifically on building capacity in clinical sites in south-eastern Europe, where rates of multi-drug resistance are particularly high.
These networks will allow the team to carry out clinical trials of a novel antibiotic combination product called Aztreonam-Avibactam (ATM-AVI). ATM-AVI is a potential option designed to tackle a sub-type of CRE infections that is especially hard to treat.
An urgent need
CREs pose a growing threat to patients and health systems in Europe and beyond. By taking steps to improve the way infections are diagnosed and treated, COMBACTE-CARE is well placed to contribute to efforts to tackle these dangerous infections.
Achievements & News
COMBACTE-CARE has recruited 2 266 patients to its EURECA study on infections that are resistant to antibiotics called carbapenems, which are considered to be among the most difficult to treat. ###In a statement, the project said: ‘Excellent collaboration between the central team and the study sites has ensured that the study has run smoothly, and in future will lead to results that have a significant impact on the practice of infectious diseases in Europe and elsewhere.’ Cases of infections caused by bacteria known as carbapanem-resistant enterobacteriaceae (CRE) are on the rise, and are most common in healthcare settings. They are extremely hard to treat (very often the only treatment options are combinations of old, toxic antibiotics) and can be fatal. The EURECA study is investigating the risk factors for CRE infection and things that influence treatment outcomes. The samples collected during the study are now being sent to a central site for analysis.
Antimicrobial resistance (AMR) project COMBACTE-CARE has recruited the first patient in the REJUVENATE study, a clinical trial of a novel antibiotic designed to tackle drug-resistant infections that are particularly hard to treat.### The goal of the REJUVENATE study is to assess the workings and safety of a novel antibiotic combination product called Aztreonam-Avibactam (ATM-AVI) in 40 hospitalised adults with ‘complicated intra-abdominal infections’. The first patient was enrolled at the University Hospital Virgen del Rocio in Seville, Spain. Other study sites recruiting patients are based in Germany and France. The COMBACTE-CARE project focuses on tackling bacteria known as ‘carbapenem-resistant enterobacteriaceae’ (CRE), which are resistant to most available antibiotics and are so difficult to treat they are considered to be an urgent global threat. Worryingly, cases of CRE infections are on the rise in Europe and globally.
Antibiotic research and development was given a boost recently by the announcement that the US Biomedical Advanced Research and Development Authority (BARDA) would fund clinical studies of a novel antibiotic combination product called Aztreonam-Avibactam (ATM-AVI). ###ATM-AVI is designed to tackle certain antibiotic infections that are particularly tough to treat. In Europe, IMI is supporting clinical studies of ATM-AVI through the COMBACTE-CARE project. The funding from BARDA will support additional studies needed to advance the development of this urgently-needed treatment.
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.’
IMI antimicrobial resistance programme expands with new project
IMI’s antimicrobial resistance programme New Drugs for Bad Bugs has acquired a new project with the launch of COMBACTE-CARE. With 18 academic partners and 3 pharmaceutical companies , the project will bring highly innovative studies and activities related to the treatment of patients with infections caused by Carbapenem-Resistant Enterobacteriaceae (CRE). ###Tough to treat and sometimes deadly, CRE are considered to be one of the most dangerous resistant bacteria in the world. Specifically, the €83 million project aims to understand how patients with CRE infections are managed, with a focus on best available treatment and clinical outcomes. The project will develop new tools to detect CRE and conduct clinical trials with AstraZeneca’s antibiotic combination product Aztreonam-Avibactam (ATM-AVI), in development for the treatment of serious infections due to a difficulty to treat sub-type of CRE infections called metallo‐β‐lactamase producing Gram‐negative pathogens. All clinical and microbiological studies will be conducted in South-Eastern Europe, where infection rates with MDR-GNB are expected to be high. The phase III study is intended to include investigation sites outside Europe to ensure the global assessment of the ATI-AVI combination product. - Read the project’s press release
ParticipantsShow participants on map
- Basilea Pharmaceutica International AG, Basel, Switzerland
- Glaxosmithkline Research And Development LTD., Brentford, Middlesex, United Kingdom
- Pfizer Limited, Sandwich, Kent , United Kingdom
Universities, research organisations, public bodies, non-profit groups
- Academisch Medisch Centrum Bij De Universiteit Van Amsterdam, Amsterdam, Netherlands
- Cardiff University, Cardiff, United Kingdom
- Centre hospitalier universitaire de Limoges, Limoges, France
- Ethniko Kai Kapodistriako Panepistimio Athinon, Athens, Greece
- Fundacion Privada Instituto De Salud Global Barcelona, Barcelona, Spain
- Institut National De La Sante Et De La Recherche Medicale, Paris, France
- Klinikum Der Universitaet Zu Koeln, Cologne, Germany
- Servicio Andaluz De Salud, Sevilla, Spain
- St George'S Hospital Medical School, London, United Kingdom
- The Foundation For Medical Research Infrastructural Development And Health Services Next To The Medical Center Tel Aviv, Tel Aviv, Israel
- The Health Corporation - Rambam, Haifa, Israel
- Universitaet Ulm, Ulm, Germany
- Universitaetsklinikum Freiburg, Freiburg, Germany
- Universitair Medisch Centrum Utrecht, Utrecht, Netherlands
- Universite De Geneve, Genève 4, Switzerland
- Universiteit Antwerpen, Antwerp, Belgium
- Centre Hospitalier Universitaire De Poitiers, Poitiers, France
- Universite De Poitiers, Poitiers , France
Non EFPIA companies
- MINISTRIA E SHENDETESISE (National Institute of Public Health of Kosovo), Pristina, Kosovo * UN resolution
- Servicio Madrileno De Salud, Madrid, Spain
|Name||IHI funding in €|
|Academisch Medisch Centrum Bij De Universiteit Van Amsterdam||250 000|
|Cardiff University||211 039|
|Centre hospitalier universitaire de Limoges||2 586 560|
|Ethniko Kai Kapodistriako Panepistimio Athinon||698 000|
|Fundacion Privada Instituto De Salud Global Barcelona||218 962|
|Institut National De La Sante Et De La Recherche Medicale||366 300|
|Klinikum Der Universitaet Zu Koeln||2 094 471|
|MINISTRIA E SHENDETESISE (National Institute of Public Health of Kosovo)||45 000|
|Servicio Andaluz De Salud||4 102 506|
|Servicio Madrileno De Salud||206 580|
|St George'S Hospital Medical School||247 500|
|The Foundation For Medical Research Infrastructural Development And Health Services Next To The Medical Center Tel Aviv||888 092|
|The Health Corporation - Rambam||522 200|
|Universitaet Ulm||121 000|
|Universitaetsklinikum Freiburg||253 000|
|Universitair Medisch Centrum Utrecht||9 521 813|
|Universite De Geneve||162 664|
|Universiteit Antwerpen||1 209 313|
|Name||Funding in €|
|Centre Hospitalier Universitaire De Poitiers||40 500|
|Universite De Poitiers||126 000|
|Total Cost||23 871 500|