Nathalie Seigneuret (IHI Scientific Project Manager for COMBACTE), Drieke Vandamme (at the time, Academic partner and Project Management Office Member of COMBACTE-MAGNET) and Mark Esser (EFPIA Partner and Management Board Member of COMBACTE-MAGNET) reflect on the COMBACTE-MAGNET project.
Nathalie Seigneuret, IHI Scientific Project Manager for COMBACTE: “COMBACTE-MAGNET focused on finding new clinical options for a highly vulnerable group of patients: those who are critically ill, undergoing intensive care and at risk for or fighting infections by Gram-negative bacteria such as Pseudomonas aeruginosa. The project delivered on its objectives.”
“The project was set up, first, to gather and analyse epidemiological data about microbial threats, drug resistance and treatment patterns across Europe” Nathalie says. “To that end, it created an epidemiological network called EPI-Net in which existing surveillance systems were connected. Various centres of excellence were created. The goal was being able to better monitor the spread of antibiotic resistance and the prevalence of healthcare-associated infections. At the patient level, it sought a better understanding of how infections affect patients’ bodies, which biomarkers reliably predict infection progress and treatment response, and why some patients respond better to treatments than others. Such knowledge allows for designing more rapid clinical trials to test innovative candidate drugs against multidrug-resistant Gram-negative bacteria, and to do so where ICU patients are most at risk. Finally, it set out to actually conduct some clinical studies to test the safety and efficacy of an antibody that might help prevent ventilator-associated pneumonia in vulnerable ICU patients, as well as that of a novel antibiotic compound.
The project delivered on its objectives. The epidemiological work carried out through the EPI-Net network and its newly created centres of excellence produced insights that will continue to support antimicrobial drug development and designs of trials using statistics and new diagnostics. The new EPI-Net surveillance database now 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 now helps international travellers, travel clinics, and infectious disease specialists navigate antimicrobial resistance risks at travel destinations and find ways to mitigate them.”
“To me, COMBACTE’s pan-European clinical network stands out as an example of how fragmentation can be reduced in clinical research. With that network having been preserved in Ecraid, future trials will continue to run better and faster, and enable new treatments to hit the market sooner.”
Nathalie adds: “The COMBACTE-MAGNET observational studies provided important new insights into current clinical management, treatment outcomes and related healthcare costs of patients with complicated Gram-negative urinary tract infections, especially in high-risk countries. Highlighting the need for strengthening patient input at all levels of the research, a toolkit was developed that provides guidance on when and how to involve the public in research and development of antimicrobials.
An important achievement was the completion of the EVADE Phase II trial of gremubamab for patients with Pseudomonas aeruginosa in their respiratory tract who need mechanical ventilation. Enrolling patients and convincing doctors to test a preemptive treatment ahead of a potential pneumonia diagnosis posed a challenge that was fully met. Although this particular trial ended up not finding a reduced incidence of nosocomial pneumonia, demonstrating an ability to test such approaches rapidly is a key project outcome.
The COMBACTE-MAGNET consortium had to adapt to various surprises along the way that affected its original workplan. Despite not being able to do all trials as initially planned, it proved how transparency and trust among all public and private partners will ultimately be the key to success. And EPI-Net’s achievements will be sustained and expanded in Ecraid.”
“While it did not lead us yet to new medications, we showed that we could design and run epidemiology and clinical trials to better understand anti-microbial resistance. We also identified risk factors and biomarkers for inflammation in urine and blood, revealed the role of the gut as a reservoir for lung infections, and developed models to measure the benefits of different interventions.”