A French integrated solution to combat antimicrobial resistance in hospitals

What is at stake

Antimicrobial resistance is a major public health issue, responsible for 35,000 deaths per year in Europe. Multidrug-resistant hospital-acquired infections affect particularly vulnerable patients and undermine essential aspects of modern medicine, particularly in intensive care and critical care. In this context, developing more effective therapeutic and diagnostic solutions is a health priority. To address this challenge, Antabio, a French biopharmaceutical company specializing in the development of innovative treatments against multidrug-resistant bacterial infections, is coordinating the DETERMINANT project alongside bioMérieux and Toulouse School of Economics.

The project

DETERMINANT (Diagnostics, Therapies, and Economic Incentives for Antimicrobial Resistance) is developing an integrated solution that combines a new antibiotic, a precision diagnostic test, and a health economic approach designed to ensure market access and the sustainability of the model.

The consortium brings together three complementary French partners: Antabio, the project leader and developer of MEM-PIL; bioMérieux, responsible for developing the associated ETEST test; and the Toulouse School of Economics, which is leading the economic modeling and valuation work. This complementarity allows the scientific, clinical, diagnostic, industrial, and economic dimensions of the project to be addressed collectively.

The ambition

The project is based on three complementary components: the MEM-PIL product, a combination of a hospital-grade antibiotic, meropenem, and an innovative resistance inhibitor, pilabactam, for the treatment of severe nosocomial infections caused by multidrug-resistant Gram-negative bacilli; the MEM-PIL ETEST, a susceptibility test that accurately measures MEM-PIL’s activity against clinical strains; and an economic model designed to demonstrate the value of these two solutions and prepare the groundwork for their market entry.

Project Innovations

DETERMINANT offers a distinctive therapeutic innovation. MEM-PIL is designed to provide broad-spectrum coverage against several priority pathogens, including carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Acinetobacter baumannii, and Pseudomonas aeruginosa, with a treatment approach tailored to either targeted or probabilistic therapy, depending on the clinical context.

The project also includes the development of an ETEST MEM-PIL diagnostic test, designed to provide a quantitative measurement of the MIC and enable more appropriate prescribing of MEM-PIL, under conditions compatible with routine microbiology laboratory practices.

Finally, DETERMINANT incorporates a health economic innovation aimed at assessing the cost of inaction in the face of resistant nosocomial infections, analyzing mechanisms to support innovation, and proposing models that reconcile the appropriate use and economic viability of MEM-PIL and the associated ETEST.

A consortium dedicated to health sovereignty

By combining therapy, diagnostics, and health economics, DETERMINANT helps strengthen France’s health and technological sovereignty in the field of antibiotic resistance and build an integrated response to a major public health challenge. IDCluster supports this initiative by acting as a project accelerator, helping to structure the project, mitigate risks, and facilitate its transition to industrial-scale production.

The MICAST® project, developed by Molsid, aims to combat antibiotic resistance, which poses a major threat to global health. The proliferation of antibiotic-resistant pathogenic bacteria is a major health crisis, currently responsible for 1.2 million direct deaths per year worldwide. It is a silent pandemic that, according to the WHO, threatens to cause 10 million deaths annually by 2052, rendering common infectious diseases incurable. Given this emergency, rapid diagnosis is vital, as each hour of inappropriate treatment increases the mortality rate of patients with sepsis by 7%, for example.

The main objective of the project is to provide an innovative and rapid antibiotic susceptibility test (antibiogram) using patented fluorogenic biotracer technology, capable of drastically reducing the time it takes to obtain results. Currently, standard disk diffusion methods, which are the most widely used by diagnostic laboratories worldwide, take a minimum of 48 hours to provide an antibiogram. MICAST®, a new-generation antibiogram, aims to reduce this time to 28 hours for standard antibiograms, effectively allowing laboratories to deliver results one day earlier, and to just 4 hours for cases of sepsis based on positive blood cultures.

This acceleration is crucial because it allows patients to be treated more quickly with effective antibiotics and reduces mortality by 20 to 30% according to studies for all types of infections and pathogens combined. The economic benefits for the healthcare system are also significant: a reduction in hospital stays of 6 days on average, representing savings of €2 million per year for a large hospital, while reducing the use of broad-spectrum antibiotics to preserve our current arsenal against the development of new resistances.

Sepsis is the body’s response to infection and affects 49 million people worldwide each year. In Europe, 3.4 million cases are reported each year, 40% of which occur in children under the age of 5, causing 680,000 deaths. Sepsis is caused mainly by bacterial (80-85%) or fungal (10-15%) infections.

The current therapeutic approach consists of administering empirical, broad-spectrum, high-dose antibiotic treatment without waiting for test results, as it is estimated that the probability of survival decreases by 7.5% for every hour of delay in effective anti-infective treatment. However, the current time required to obtain information identifying the pathogen and its possible resistance to antibiotics exceeds 12 to 24 hours.

This probabilistic treatment proves ineffective in 35% of cases and has significant side effects for surviving patients: more than 60% of them suffer from post-sepsis syndromes (PSS): repeated infections, organ dysfunction, cognitive decline, depression, etc.

This suboptimal use of antimicrobials has contributed to the selection of (multi)resistant bacteria and their spread among humans, livestock, and the environment.

The fight against antimicrobial resistance (AMR) has been a priority for the WHO since 2017 due to the risk of new pandemics emerging.

The ICARRE project, led by the startup Weezion, the Hospices Civils de Lyon, and Claude Bernard Lyon 1 University, aims to develop and bring to the clinical testing phase a rapid diagnostic solution for bacterial and fungal infections responsible for sepsis and their resistance to antimicrobials.

Through the development of Weezion DX, the first rapid, all-in-one, 100% automated diagnostic tool, the ICARRE project aims to: 

– enable a diagnosis to be delivered in 60-90 minutes, including the identification of pathogens covering more than 98% of epidemiology, the broad detection of antimicrobial resistance mechanisms for more than 98% of first-line molecule resistance mechanisms, categorize the pathogen as S/R (sensitive or resistant) with a prediction of the MIC (Minimum Inhibitory Concentration), all at a competitive cost of less than €50 per test, deployable on blood cultures for bacteremia and fungemia, and on isolates for other infectious locations.

– Improve patient care by introducing appropriate treatment more quickly: de-escalate (reducing post-sepsis syndromes, hospitalization costs, and combating antimicrobial resistance) or escalate (effective treatment increasing patient survival rates). 

– Help set up an integrated epidemiological surveillance tool for resistance to anticipate the emergence of new pandemics.

According to scientific publications, the savings generated by the routine use of Weezion DX will reduce hospital stays by 20% and PSS by 25%, resulting in savings of €2 billion per year for the French healthcare system alone.

The project builds on a long and fruitful history of collaboration between the three partners. They will benefit from the support of Infectious Disease Cluster to accelerate the market launch of Weezion DX and its deployment in hospital platforms across France, Europe, and worldwide.