Impact on: Antimicrobial Resistance - the legacy of the COMBACTE projects

What's the problem?

The widespread use of antibiotics to combat bacterial infections in both humans has positively influenced our way of life in many ways. However, overuse of these drugs has led to a sharp rise in the number of bacteria that can resist them – the WHO estimates that bacterial AMR was directly responsible for 1.27 million deaths in 2019 and contributed to 4.95 million deaths worldwide. The spread of antimicrobial resistant pathogens are especially dangerous because they threaten our ability to treat common infections and to perform life-saving medical procedures like surgery and chemotherapy.

However, it is extremely challenging to develop new antimicrobials that can fight back against these drug-resistant bacteria. It can take up to 15 years and more than €900 000 000 to develop a new antibiotic, and no new classes of antibiotics have reached the market since the 1980s.

What are we doing about it?

IMI kicked off the New Drugs for Bad Bugs programme in 2013, which aimed to tackle AMR from four different angles:

Getting the drug into the bug
Translating results from early discovery to the clinic, combining expertise from industry and academia to work on new early-stage molecules
Clinical development: creating sustainable networks relating to clinical trials and running clinical trials and studies
Investigating options for a new economic model of antibiotic development and stewardship.

The COMBACTE projects were focused on the third pillar.

IHI / IMI research...

…performed clinical trials of new potential treatments for infections caused by antimicrobial resistance

The COMBACTE-CARE project paved the way towards the development of new, innovative treatments to tackle dangerous Gram-negative bacteria. Two clinical trials supported by COMBACTE-CARE – REVISIT and REJUVENATE – contributed to the successful development of the EMBLAVEO® drug which was approved for marketing authorisation by the European Commission in 2024. This treatment will provide relief to patients suffering with serious intra-abdominal and urinary tract infections, hospital-acquired pneumonia and other infections caused by Gram-negative bacteria. COMBACTE-NET also ran a phase II clinical trial (SAATELLITE) on a monoclonal antibody targeting Staphylococcus aureus and COMBACTE-MAGNET ran a phase II clinical trial (EVADE) on a monoclonal antibody targeting the Pseudomonas aeruginosa bacteria, both involving critically-ill patients at risk of serious life-threatening infections.

…built a European network of research clinics, laboratories and investigators to rapidly evaluate novel antimicrobial agents

The COMBACTE-NET project successfully set up CLIN-Net, a network of more than 1200 hospitals that can quickly and reliably recruit patients for clinical trials for new AMR drugs; and LAB-Net, a network of more than 900 microbiology laboratories that can rapidly deliver robust, standardised data on microbial strains and their resistance against existing drugs. The project also set up STAT-Net, linking statistical experts from both academics and industry who work with pharmacokinetics/pharmacodynamics, modelling, biostatistics, epidemiology and more. The value of the networks set up by the COMBACTE-Net project was proven in the Phase II and Phase III clinical trials run in the COMBACTE projects (SAATELLITE, EVADE, REJUVENATE and REVISIT)

…created an epidemiological network that connected surveillance systems for microbial threats in Europe

The EPI-Net network was set up under COMBACTE-MAGNET to monitor the spread of antimicrobial resistance throughout Europe, and especially outbreaks that occurred in hospital and healthcare settings. Centres of excellence were established and data shared. The surveillance database currently provides up-to-date, Europe-wide information on the prevalence and incidence of hospital-acquired infections and the spread of antimicrobial resistance. An online AMR Travel Tool also helps international travellers, travel clinics, and infectious disease specialists navigate antimicrobial resistance risks at travel destinations and find ways to mitigate them.

…investigated how bacterial infections affect different people's bodies.

The COMBACTE-MAGNET project investigated how bacterial infections affect patient’s bodies in more detail, outlined which biomarkers could reliably predict infection progress and treatment response, and sought to better understand why some people respond better to drugs than others.

Achievements

Event: impact on AMR - the legacy of COMBACTE

IHI and IMI are presenting a webinar showcasing the work that the COMBACTE projects have done to combat AMR.