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.