Utvikling av antibiotika resistens hemmere

Offentlig prosjektsammendrag

Antimicrobial Multidrug Resistance (AMR) is an emerging and devastating global health problem caused directly by over-use of antibiotics. AMR jeopardizes our ability to perform many life-saving procedures such as surgery and cancer chemotherapy, as well as treating life-threatening infections. This project addresses this silent pandemic by developing a product that inhibits a key bacteria resistance mechanism, restoring antibiotic efficacy against bacterial infections. Carbapenemases are enzymes produced by bacteria to destroy carbapenems (antibiotics), conferring antibiotic resistance to potentially deadly bacteria. The main carbapenemase families are serine-beta-lactamases (SBL) and metallo-beta-lactamases (MBL). Beta-lactamase inhibitors (BLI) target these enzymes, rendering the antibiotics sensitive towards the bacteria again. Our innovation is a discovery of a new class of molecules, including lead candidates APC148/247, that restore the efficacy of carbapenems by inactivating the MBL and SBL enzymes. In this project we will test APC148/247 and meropenem (antibiotic) efficacy in the laboratory on many different resistant bacteria strains obtained from patients. We will then test the safety of APC148/247 on cells and in animals, alone and in combination with meropenem. If the efficacy is satisfactory and with acceptable side effects, APC148/247 and meropenem will be tested in healthy volunteers and patients to find the optimal doses. The final clinical testing will be in a large numbers of patients comparing our product to standard-of-care treatment, to document the usefulness of the product. As part of this project we will develop a commercial product suitable for intravenous infusion to the patient, a scaleable manufacturing process of APC148/247 and maintain our patents in many countries all over the world.